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Journal articles on the topic "Insuline – Agonistes"
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Ye, Ji-Ming, Miguel A. Iglesias, David G. Watson, Bronwyn Ellis, Leonie Wood, Per Bo Jensen, Rikke Veggerby Sørensen, et al. "PPARα/γ ragaglitazar eliminates fatty liver and enhances insulin action in fat-fed rats in the absence of hepatomegaly." American Journal of Physiology-Endocrinology and Metabolism 284, no. 3 (March 1, 2003): E531—E540. http://dx.doi.org/10.1152/ajpendo.00299.2002.
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Peroxisome proliferator-activated receptor (PPAR)α and PPARγ agonists lower lipid accumulation in muscle and liver by different mechanisms. We investigated whether benefits could be achieved on insulin sensitivity and lipid metabolism by the dual PPARα/γ agonist ragaglitazar in high fat-fed rats. Ragaglitazar completely eliminated high-fat feeding-induced liver triglyceride accumulation and visceral adiposity, like the PPARα agonist Wy-14643 but without causing hepatomegaly. In contrast, the PPARγ agonist rosiglitazone only slightly lessened liver triglyceride without affecting visceral adiposity. Compared with rosiglitazone or Wy-14643, ragaglitazar showed a much greater effect (79%, P< 0.05) to enhance insulin's suppression of hepatic glucose output. Whereas all three PPAR agonists lowered plasma triglyceride levels and lessened muscle long-chain acyl-CoAs, ragaglitazar and rosiglitazone had greater insulin-sensitizing action in muscle than Wy-14643, associated with a threefold increase in plasma adiponectin levels. There was a significant correlation of lipid content and insulin action in liver and particularly muscle with adiponectin levels ( P < 0.01). We conclude that the PPARα/γ agonist ragaglitazar has a therapeutic potential for insulin-resistant states as a PPARγ ligand, with possible involvement of adiponectin. Additionally, it can counteract fatty liver, hepatic insulin resistance, and visceral adiposity generally associated with PPARα activation, but without hepatomegaly.
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Yajima, Ken, Hiroshi Hirose, Haruhisa Fujita, Yoshiko Seto, Hiroshi Fujita, Kaname Ukeda, Kiichi Miyashita, et al. "Combination therapy with PPARγ and PPARα agonists increases glucose-stimulated insulin secretion in db/dbmice." American Journal of Physiology-Endocrinology and Metabolism 284, no. 5 (May 1, 2003): E966—E971. http://dx.doi.org/10.1152/ajpendo.00149.2002.
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Although peroxisome proliferator-activated receptor (PPAR)γ agonists ameliorate insulin resistance, they sometimes cause body weight gain, and the effect of PPAR agonists on insulin secretion is unclear. We evaluated the effects of combination therapy with a PPARγ agonist, pioglitazone, and a PPARα agonist, bezafibrate, and a dual agonist, KRP-297, for 4 wk in male C57BL/6J mice and db/db mice, and we investigated glucose-stimulated insulin secretion (GSIS) by in situ pancreatic perfusion. Body weight gain in db/db mice was less with KRP-297 treatment than with pioglitazone or pioglitazone + bezafibrate treatment. Plasma glucose, insulin, triglyceride, and nonesterified fatty acid levels were elevated in untreated db/db mice compared with untreated C57BL/6J mice, and these parameters were significantly ameliorated in the PPARγ agonist-treated groups. Also, PPARγ agonists ameliorated the diminished GSIS and insulin content, and they preserved insulin and GLUT2 staining in db/db mice. GSIS was further increased by PPARγ and -α agonists. We conclude that combination therapy with PPARγ and PPARα agonists may be more useful with respect to body weight and pancreatic GSIS in type 2 diabetes with obesity.
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Kim Jun, Jeany. "Focus on New Diabetes Treatment Options with Cardiovascular Benefits." Journal of Contemporary Pharmacy Practice 66, no. 3 (September 1, 2019): 34–40. http://dx.doi.org/10.37901/jcphp18-00029.
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The landscape of diabetes treatment options has changed due to new diabetes drug approvals, changes in the Food and Drug Administration indications based on cardiovascular (CV) outcomes studies, as well as the approval of follow-on biologic insulins. Two new drugs were approved for type 2 diabetes mellitus including ertugliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and semaglutide, a glucagon-like peptide-1 (GLP1) receptor agonist joining a number of other drugs in these classes. In addition, follow-on biologic insulins, such as long-acting Basaglar (insulin glargine), and rapid-acting insulins Admelog (insulin lispro) and Fiasp (insulin aspart), were also approved. Furthermore, the CV outcome trial for dapagliflozin was published in November 2018 showing CV benefits. Finally, the 2018 joint American Diabetes Association (ADA) and European Association for the Study of Diabetes statement on the management of type 2 diabetes and the 2019 ADA Standards of Care for Diabetes made several recommendations. They encourage the use of agents with CV benefit in those with established atherosclerotic cardiovascular disease (ASCVD) or heart failure and to consider GLP1 receptor agonists as the first injectable agent, even before basal insulin, in certain patients. The purpose of this review is to discuss recently approved agents for type 2 diabetes comparing the available cardiovascular findings of SGLT2 inhibitors and GLP1 receptor agonists and outline key take-home points when recommending additional treatment for patients with type 2 diabetes after metformin.
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Cresser, Justin, Arend Bonen, Adrian Chabowski, Leslie E. Stefanyk, Roberto Gulli, Ian Ritchie, and David J. Dyck. "Oral administration of a PPAR-δ agonist to rodents worsens, not improves, maximal insulin-stimulated glucose transport in skeletal muscle of different fibers." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 299, no. 2 (August 2010): R470—R479. http://dx.doi.org/10.1152/ajpregu.00431.2009.
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Agonists targeting the nuclear receptor peroxisome proliferator-activated receptors (PPAR)-δ may be potential therapeutic agents for insulin-resistant related conditions, as they may be able to stimulate fatty acid (FA) oxidation and attenuate the accumulation of harmful lipid species in skeletal muscle. Several reports have demonstrated that PPAR-δ agonists improve whole body insulin sensitivity. However, whether these agonists exert their direct effects on glucose and FA metabolism in skeletal muscle, and specifically with different fiber types, is unknown. This study was undertaken to determine the effects of oral treatment with the PPAR-δ agonist, GW 501516, in conjunction with the administration of a high-saturated-fat diet on insulin-stimulated glucose transport in isolated oxidative (soleus) and glycolytic (epitrochlearis) rodent skeletal muscle in vitro. High-fat feeding significantly decreased maximal insulin-stimulated glucose transport in soleus, but not epitrochlearis muscle, and was associated with increased skeletal muscle diacylglycerol and ceramide content. Unexpectedly, treatment with the PPAR-δ agonist significantly reduced insulin-stimulated glucose transport in both soleus and epitrochlearis muscles, regardless of dietary fat content. The reduction in insulin-stimulated glucose transport induced by the agonist was associated with large increases in total muscle fatty acid translocase (FAT)/CD36protein content, but not diacylglycerol or ceramide contents. Agonist treatment did not alter the protein content of PPAR-δ, GLUT4, or insulin-signaling proteins (IRS-1, p85 PI3-K, Akt). Agonist treatment led to a small, but significant increase, in the oxidative capacity of glycolytic but not oxidative muscle. We propose that chronic treatment with the PPAR-δ agonist GW 501516 may induce or worsen insulin resistance in rodent skeletal muscle by increasing the capacity for FA transport across the sarcolemma without a sufficient compensatory increase in FA oxidation. However, an accumulation of diacylglycerol and ceramide, while associated with diet-induced insulin resistance, does not appear to be responsible for the agonist-induced reduction in insulin-stimulated glucose transport.
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Zhang, Xianyang, Tengjiao Cui, Jinlin He, Haibo Wang, Renzhi Cai, Petra Popovics, Irving Vidaurre, et al. "Beneficial effects of growth hormone-releasing hormone agonists on rat INS-1 cells and on streptozotocin-induced NOD/SCID mice." Proceedings of the National Academy of Sciences 112, no. 44 (October 16, 2015): 13651–56. http://dx.doi.org/10.1073/pnas.1518540112.
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Agonists of growth hormone-releasing hormone (GHRH) have been previously reported to promote growth, function, and engraftment of islet cells following transplantation. Here we evaluated recently synthesized GHRH agonists on the proliferation and biological functions of rat pancreatic β-cell line (INS-1) and islets. In vitro treatment of INS-1 cells with GHRH agonists increased cell proliferation, the expression of cellular insulin, insulin-like growth factor-1 (IGF1), and GHRH receptor, and also stimulated insulin secretion in response to glucose challenge. Exposure of INS-1 cells to GHRH agonists, MR-356 and MR-409, induced activation of ERK and AKT pathways. Agonist MR-409 also significantly increased the levels of cellular cAMP and the phosphorylation of cAMP response element binding protein (CREB) in INS-1 cells. Treatment of rat islets with agonist, MR-409 significantly increased cell proliferation, islet size, and the expression of insulin. In vivo daily s.c. administration of 10 μg MR-409 for 3 wk dramatically reduced the severity of streptozotocin (STZ)-induced diabetes in nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice. The maximal therapeutic benefits with respect to the efficiency of engraftment, ability to reach normoglycemia, gain in body weight, response to high glucose challenge, and induction of higher levels of serum insulin and IGF1 were observed when diabetic mice were transplanted with rat islets preconditioned with GHRH agonist, MR-409, and received additional treatment with MR-409 posttransplantation. This study provides an improved approach to the therapeutic use of GHRH agonists in the treatment of diabetes mellitus.
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Cariou, Bertrand, Narimène Belhatem, Esteban Jodar, Stewart Harris, Elmar Jaeckel, Ildiko Lingvay, keval Chandrana, Trine Abrahamsen, and Christopher Sorli. "Impact de l’IMC sur la réduction de l’HbA 1c sous IDegLira chez des diabétiques de type 2 insuffisamment contrôlés sous sulfamides, agonistes des récepteurs au GLP-1 ou insuline Glargine U100 : analyses d’études de phase IIIb." Diabetes & Metabolism 43, no. 2 (March 2017): A114. http://dx.doi.org/10.1016/s1262-3636(17)30437-8.
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Chang, Feng, Linda A. Jaber, Helen D. Berlie, and Mary Beth O'Connell. "Evolution of Peroxisome Proliferator-Activated Receptor Agonists." Annals of Pharmacotherapy 41, no. 6 (June 2007): 973–83. http://dx.doi.org/10.1345/aph.1k013.
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OBJECTIVE: To discuss the evolution of peroxisome proliferator-activated receptor (PPAR) agonists from single site to multiple subtype or partial agonists for the treatment of type 2 diabetes, dyslipidemia, obesity, and the metabolic syndrome. DATA SOURCES: Information was obtained from MEDLINE (1966-March 2007) using search terms peroxisome proliferator-activated receptor agonist, PPAR dual agonist, PPAR α/γ agonist, PPAR pan agonist, partial PPAR, and the specific compound names. Other sources included pharmaceutical companies, the Internet, and the American Diabetes Association 64th-66th Scientific Sessions abstract books. STUDY SELECTION AND DATA EXTRACTION: Animal data, abstracts, clinical trials, and review articles were reviewed and summarized. DATA SYNTHESIS: PPAR α, γ, and δ receptors play an important role in lipid metabolism, regulation of adipocyte proliferation and differentiation, and insulin sensitivity. The PPAR dual agonists were developed to combine the triglyceride lowering and high-density lipoprotein cholesterol elevation from the PPAR-α agonists (fibrates) with the insulin sensitivity improvement from the PPAR-γ agonists (thiazolidinediones). Although the dual agonists reduced hemoglobin A1C(A1C) and improved the lipid profile, adverse effects led to discontinued development. Currently, PPAR-γ agonists (GW501516 in Phase I trials), partial PPAR-γ agonists (metaglidasen in Phase II and III trials), and pan agonists (α, γ, δ netoglitazone in Phase II and III trials) with improved cell and tissue selectivity are undergoing investigation to address multiple aspects of the metabolic syndrome with a single medication. By decreasing both A1C and triglycerides, metaglidasen did improve multiple aspects of the metabolic syndrome with fewer adverse effects than compared with placebo. Metaglidasen is now being compared with pioglitazone. CONCLUSIONS: Influencing the various PPARs results in improved glucose, lipid, and weight management, with effects dependent on full or partial agonist activity at single or multiple receptors. Although the dual PPAR compounds have been associated with unacceptable toxicities, new PPAR agonist medications continue to be developed and investigated to discover a safe drug with benefits in multiple disease states.
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Porskjær Christensen, Lars, and Rime Bahij El-Houri. "Development of an In Vitro Screening Platform for the Identification of Partial PPARγ Agonists as a Source for Antidiabetic Lead Compounds." Molecules 23, no. 10 (September 22, 2018): 2431. http://dx.doi.org/10.3390/molecules23102431.
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Type 2 diabetes (T2D) is a metabolic disorder where insulin-sensitive tissues show reduced sensitivity towards insulin and a decreased glucose uptake (GU), which leads to hyperglycaemia. Peroxisome proliferator-activated receptor (PPAR)γ plays an important role in lipid and glucose homeostasis and is one of the targets in the discovery of drugs against T2D. Activation of PPARγ by agonists leads to a conformational change in the ligand-binding domain, a process that alters the transcription of several target genes involved in glucose and lipid metabolism. Depending on the ligands, they can induce different sets of genes that depends of their recruitment of coactivators. The activation of PPARγ by full agonists such as the thiazolidinediones leads to improved insulin sensitivity but also to severe side effects probably due to their behavior as full agonists. Partial PPARγ agonists are compounds with diminished agonist efficacy compared to full agonist that may exhibit the same antidiabetic effect as full agonists without inducing the same magnitude of side effects. In this review, we describe a screening platform for the identification of partial PPARγ agonists from plant extracts that could be promising lead compounds for the development of antidiabetic drugs. The screening platform includes a series of in vitro bioassays, such as GU in adipocytes, PPARγ-mediated transactivation, adipocyte differentiation and gene expression as well as in silico docking for partial PPARγ agonism.
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Montessuit, Christophe, Irène Papageorgiou, and René Lerch. "Nuclear Receptor Agonists Improve Insulin Responsiveness in Cultured Cardiomyocytes through Enhanced Signaling and Preserved Cytoskeletal Architecture." Endocrinology 149, no. 3 (December 6, 2007): 1064–74. http://dx.doi.org/10.1210/en.2007-0656.
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Insulin resistance is the failure of insulin to stimulate the transport of glucose into its target cells. A highly regulatable supply of glucose is important for cardiomyocytes to cope with situations of metabolic stress. We recently observed that isolated adult rat cardiomyocytes become insulin resistant in vitro. Insulin resistance is combated at the whole body level with agonists of the nuclear receptor complex peroxisome proliferator-activated receptor γ (PPARγ)/retinoid X receptor (RXR). We investigated the effects of PPARγ/RXR agonists on the insulin-stimulated glucose transport and on insulin signaling in insulin-resistant adult rat cardiomyocytes. Treatment of cardiomyocytes with ciglitazone, a PPARγ agonist, or 9-cis retinoic acid (RA), a RXR agonist, increased insulin- and metabolic stress-stimulated glucose transport, whereas agonists of PPARα or PPARβ/δ had no effect. Stimulation of glucose transport in response to insulin requires the phosphorylation of the signaling intermediate Akt on the residues Thr308 and Ser473 and, downstream of Akt, AS160 on several Thr and Ser residues. Phosphorylation of Akt and AS160 in response to insulin was lower in insulin-resistant cardiomyocytes. However, treatment with 9-cis RA markedly increased phosphorylation of both proteins. Treatment with 9-cis RA also led to better preservation of microtubules in cultured cardiomyocytes. Disruption of microtubules in insulin-responsive cardiomyocytes abolished insulin-stimulated glucose transport and reduced phosphorylation of AS160 but not Akt. Metabolic stress-stimulated glucose transport also involved AS160 phosphorylation in a microtubule-dependent manner. Thus, the stimulation of glucose uptake in response to insulin or metabolic stress is dependent in cardiomyocytes on the presence of intact microtubules.
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Balakumar, Pitchai, Nanjaian Mahadevan, and Ramanathan Sambathkumar. "A Contemporary Overview of PPARα/γ Dual Agonists for the Management of Diabetic Dyslipidemia." Current Molecular Pharmacology 12, no. 3 (July 29, 2019): 195–201. http://dx.doi.org/10.2174/1874467212666190111165015.
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Background: Diabetes mellitus and concomitant dyslipidemia, being referred to as ‘diabetic dyslipidemia’, are the foremost detrimental factors documented to play a pivotal role in cardiovascular illness. Diabetic dyslipidemia is associated with insulin resistance, high plasma triglyceride levels, low HDL-cholesterol concentration and elevated small dense LDL-cholesterol particles. Maintaining an optimal glucose and lipid levels in patients afflicted with diabetic dyslipidemia could be a major task that might require a well-planned diet-management system and regular physical activity, or otherwise an intake of combined antidiabetic and antihyperlipidemic medications. Synchronized treatment which efficiently controls insulin resistance-associated diabetes mellitus and co-existing dyslipidemia could indeed be a fascinating therapeutic option in the management of diabetic dyslipidemia. Peroxisome proliferator-activated receptors α/γ (PPARα/γ) dual agonists are such kind of drugs which possess therapeutic potentials to treat diabetic dyslipidemia. Nevertheless, PPARα/γ dual agonists like muraglitazar, naveglitazar, tesaglitazar, ragaglitazar and aleglitazar have been reported to have undesirable adverse effects, and their developments have been halted at various stages. On the other hand, a recently introduced PPARα/γ dual agonist, saroglitazar is an emerging therapeutic agent of glitazar class approved in India for the management of diabetic dyslipidemia, and its treatment has been reported to be generally safe and well tolerated. Conclusion: Some additional and new compounds, at initial and preclinical stages, have been recently reported to possess PPARα/γ dual agonistic potentials with considerable therapeutic efficacy and reduced adverse profile. This review sheds light on the current status of various PPARα/γ dual agonists for the management of diabetic dyslipidemia.
Dissertations / Theses on the topic "Insuline – Agonistes"
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Lavigne, Charles. "Effets de la nature des protéines alimentaires sur la prévention de la résistance à l'insuline chez le rat." Thesis, Université Laval, 2006. http://www.theses.ulaval.ca/2006/23771/23771.pdf.
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Dubois, Mathilde. "Dysfonctionnement des cellules β au cours du diabète de type 2 : rôle de la glucotoxicité et de la lipotoxicité et influence du Peroxisome Proliferator-Activated Receptor γ." Lille 2, 2003. http://www.theses.fr/2003LIL2P009.
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Silva, Silvana Auxiliadora Bordin da. "Mecanismos ionicos envolvidos na regulação da secreção de insulina por agonistas muscarinicos." [s.n.], 1995. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313942.
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Orientadores: Antonio Carlos Boschero, Antonio Ari GonçalvesTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-07-21T02:38:56Z (GMT). No. of bitstreams: 1 Silva_SilvanaAuxiliadoraBordinda_D.pdf: 7203388 bytes, checksum: c77a4e34c567f2a9f3b4744751eab31c (MD5) Previous issue date: 1995
Resumo: O presente trabalho teve como proposta caracterizar o subtipo funcional de mAChR na célula ß pancreática, bem como elucidar os mecanismos iônicos envolvidos na estimulação muscarínica. Para isto, foram utilizadas ilhotas de ratos e camundongos, isoladas por digestão enzimática ou microdissecção. A resposta celular frente a estimulação pelo agonista muscarínico OXO-M foi analisada sob diferentes aspectos: (1) secreção de insulina; (2) efluxo de radioisótopos (45Ca e 86Rb); (3) concentração citoplasmática de Ca2+ ([Ca2+]i); (4) atividade elétrica; e (5) expressão dos mAChRs. Os resultados mostram que OXO-M aumentou, de forma dose-dependente, a secreção de insulina por ilhotas de roedores. Na presença de alta concentração (50 µM), OXO-M induziu uma resposta bifásica da secreção, tanto na presença de 5,6 quanto de 16,7 mM de glicose. O aumento da secreção induzido pela OXO-M foi drasticamente reduzido pela retirada de Ca2+ do meio perfusor, e completamente abolido na ausência de glicose. Entretanto, na ausência de glicose mas na presença de K+ em concentração despolarizante (40 mM), OXO-M aumentou significativamente a secreção de insulina. O efeito potencializador da OXO-M foi inibido pelos antagonistas 4-DAMP (M3); p-F-HHSiD (M3>M1>M2) e pirenzepina (M1) com valores de IC50 para estes antagonistas de ~ 5, 20 e 340 nM, respectivamente. A análise molecular do subtipo de mAChR expresso nas ilhotas pancreáticas, realizada pela amplificação do cDNA por PCR, demonstrou a presença dos subtipos M1 e M3 no tecido. Entretanto, o estudo farmacológico indicou que o subtipo M3 representa o receptor muscarínico que medeia a estimulação da célula ß. Em outra série de experimentos, foram estudados os movimentos iônicos envolvidos na estimulação celular induzida pela OXO-M. Na presença de 5,6, 11,2 ou na ausência de glicose, OXO-M aumentou a [Ca2+]i de células ß isoladas. Este aumento foi parcialmente inibido pela adição de EGT A no meio de perfusão. OXO-M (50 µM) também aumentou o efluxo de 45Ca de ilhotas perfundidas, tanto na presença quanto na ausência de Ca2+ no meio extracelular. Entretanto, na ausência de Ca2+ (condição que representa o fluxo unidirecional provindo de compartimentos intracelulares), o aumento no efluxo foi transiente. A curva obtida pela diferença entre os efluxos normalizados, em ambas as condições experimentais, demonstrou a presença de um segundo componente, de aparecimento tardio e provavelmente decorrente da entrada de Ca2+ nas células. Tanto na presença quanto na ausência de glicose, OXO-M aumentou o efluxo do 86Rb. OXO-M também aumentou a atividade elétrica induzida pela glicose. Em 11,2 mM de glicose, OXO-M (0,1 e 10 µM) produziu diferentes efeitos sobre a atividade elétrica. Em ambas as concentrações, o agonista provocou o aumento na freqüência de bursts. Por outro lado, em presença de concentrações micromolares OXO-M induziu alterações multifásicas na atividade elétrica, caracterizada pela inibição transiente da atividade elétrica (i.e., polarização da membrana), seguida pelo aumento na freqüência de bursts e por uma pequena despolarização da membrana na fase silente. O efeito polarizante da OXO-M foi inibido pela ChTX, um bloqueador dos canais de K+ ativados por Ca2+ (KCa). A permeabilidade ao K+, calculada a partir dos valores de efluxo do 86Rb e de potencial de membrana, aumentou durante a fase de polarização, mas não foi diferente do controle durante o estado estacionário. Concluindo, o efeito potencializador da OXO-M sobre a secreção de insulina induzida pela glicose depende da ativação dos receptores muscarínicos do subtipo M3, presentes na membrana da célula ß. Semelhante ao observado na estimulação por outros agonistas (p.e., ACh e CCh), o aumento na secreção depende da presença de glicose e Ca2+ no meio extracelular. A polarização transiente induzida por concentrações micromolares de OXO-M representa a ativação dos canais KCa. Por outro lado, a permeabilidade ao K+ no período estacionário indica que a despolarização da membrana não é conseqüência do bloqueio de canais de K+, mas provavelmente da ativação de uma corrente sensível aos níveis intracelulares de Ca2+ (CRAC). Assim, o balanço entre a ativação dos canais KCa e CRAC poderiam determinar o grau de despolarização induzi da por agonistas muscarínicos, mecanismo este provavelmente importante na modulação da secreção de insulina durante a estimulação colinérgica
Abstract: The effects of the muscarinic agonist oxotremorine-m (OXO-M) on insulin secretion, 45Ca and 86Rb fluxes, cytosolic Ca2+ concentration ([Ca2+]i), and electrical activity in pancreatic rodent ß-cells were studied. ln the presence of glucose, OXO-M produced a dose-dependent potentiation of insulin secretion from rat and mouse islets. Higher doses of OXO-M (50 µM) induced a biphasic insulin response, both at low (5.6 mM) or high (16.7 mM) glucose concentration. ln a Ca2+-deficient medium containing glucose (5.6 mM), OXO-M evoked only a reduced first phase of insulin secretion. ln the absence of glucose, OXO-M (up to 200 µM) did not effected basal secretion. However, in the absence of glucose, but at a depolarizing K+ concentration (40 mM), OXO-M significantly increased insulin release from incubated islets. The potentiating effects of OXO-M were inhibited by the muscarinic receptor antagonists 4-DAMP (M3), p-F-HHSiD (M3> M1>M2), and pirenzepine (M1) in a dose-dependent manner; half maximal inhibitory concentration values were ~ 5, 20, and 340 nM, respectively. cDNAs encoding for M1 and M3 muscarinic acetylcholine receptors (mAChRs) were detected in rat pancreatic islet cells by polimerase chain reaction (PCR) amplification techniques. The PCR products showed bands with the expected base pair number corresponding to M1 and M3 selected sequences. ln other series of experiments, we studied the ionic movements under muscarinic stimulation. At zero, 5.6 or 11.2 mM glucose, OXO-M increased the [Ca2+]i in isolated ß-cells. The increment in the [Ca2+]i was partially inhibited by the addition of EGTA in the perifusion medium. OXO-M (50 µM) also increased 45Ca efflux from islets perifused either in the presence or in the absence of Ca2+. However, under the latter condition, the efllux (which reflects intracellular Ca2+ mobilization) was transient. The normalized difference between emuxes revealed the presence of a delayed and sustained second component, originating from the extracellular space. Either in presence or absence of glucose, OXO-M increased 86Rb efflux. OXO-M also produced a dose-dependent increase on the glucoseinduced electrical activity. At 11.2 mM glucose, OXO-M (0.1 and 10 µM) had two distinct effects: both concentrations increased the steady-state burst frequency; however, micromolar concentrations of OXO-M induced a multiphasic change in the pattern of electrical activity, including a transient inhibition of electrical activity and then a phase of high burst frequency, which was accompanied by a small depolarization in the membrane during the silent phase. The polarizing effect of OXO-M was almost completely suppressed by charibdotoxin (ChTX), a blocker of the large conductance [Ca2+ ]i ¿ activated potassium channel (KCa). K+-permeability values, calculated from 86Rb efflux and electrical measurements, increased during the polarizing phase, but was not different from control values (no OXO-M) during the steady state period. In conclusion, the potentiation of glucose-induced insulin secretion by OXO-M depends on the activation of a muscarinic M3 receptor subtype, present in the ß-cell plasma membrane. As already observed for others muscarinic agonists, such as ACh and CCh, OXO-M potentiated-insulin secretion depends on the presence of suitable amount of glucose and Ca2+ in the extracellular medium. The rapid and transient polarization induced by OXO-M (over 1 µM) represents the activation of the maxi K+-channel. As OXO-M did not changed K+ permeability during the steady-state period, the depolarizing effect of OXO-M does not reflects a decrease in K+-permeability. Instead, it may be the consequence of activation of a current sensitive to the depletion of intracellular Ca2+ stores (CRAC). Thus, the balance between the activation of KCa channel and CRAC could dictate the degree of depolarization induced by muscarinic agonists. Finally, although the KCa channel was not implicated in the repolarization of glucose-induced electrical activity in ß-cells, our results support the idea that the maxi K+-channel could play a role in the cholinergic modulation of insulin secretion
Doutorado
Fisiologia e Biofisica
Doutor em Ciências
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Yimlamai, Tossaporn. "The effects of hindlimb unweighting and beta2-agonist on the ubiquitin-proteasome pathway and insulin-like growth factor i." [Gainesville, Fla.] : University of Florida, 2004. http://purl.fcla.edu/fcla/etd/UFE0003660.
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Freitas, Fatima Rodrigues de Sousa e. "Efeito da reposição do hormônio do crescimento (GH) no desenvolvimento ósseo de ratas hipotireoideas tratadas com o agonista seletivo do receptor b de hormônio tireoideano GC-1." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-08092008-115022/.
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Sabe-se que o hipotireoidismo (Hipo) resulta em supressão do eixo hormônio de crescimento (GH)/ insulin-like growth factor I (IGF-I) e em atraso no desenvolvimento esquelético. Em um estudo anterior, vimos que o tratamento de ratas jovens Hipo com GC-1, um análogo da triiodotironina (T3) seletivo pela isoforma b de receptor de hormônio tireoideano (TRb), não teve efeito sobre o IGF-I sérico ou sobre a expressão protéica de IGF-I nas lâminas epifisiais, mas parcialmente reverteu alterações esqueléticas decorrentes do Hipo, o que sugere que: (i) o desenvolvimento esquelético requer ações do T3 mediadas pelo TRa1 e TRb1 (isoformas de TR expressas no osso); ou (ii) requer interações entre o eixo GH/IGF-I e o hormônio tireoideano. Neste estudo, investigamos essas hipóteses tratando ratas recém desmamadas Hipo com T3 ou GC-1 em associação ou não com o GH por 4 semanas. Os nossos achados mostram que o T3 e GH interagem para promover o desenvolvimento ósseo, mas que uma série de efeitos do T3 nesse processo independe do eixo GH/IGF-I e são mediadas pelo TRa e/ou TRb.Thyroid hormone (TH) has important effects on bone development and metabolism. It is known that triiodotyronine (T3) has indirect actions in the skeleton through its influence on the production and secretion of growth hormone (GH)/ insulin-like growth factor (IGF-I) and/or other factors. On the other hand, direct actions of T3 on bone are recognized but not yet clear. Most of T3 action is mediaded by its nuclear receptors (TRs). TRa1, TRb1 e TRb2 bind T3, while TRa2 does not bind T3 and acts as an antagonist of genic transcription of TRa1 and TRb1. All these receptors, except TRb2, are expressed in chondrocytes of growth plate, osteoblasts and osteoclastos. However, the functional roles of each TR isoformas in the bone development are incompletely understood. A few years, it is development GC-1, a synthetic analog of T3 which is selectivwe for TRb1 over TRa1. In recent study, we showed that treatment of hypothyroid young rats with T3 revert the IGF-I deficiency and skeleton defects caused by hypothyroidism. Since GC-1 treatment does not effects on serum levels of IGF-I or protein expression of IGF-I in the growth plate, but revert some bone alterations induced by T3 deficiency. Considering the selectivity of GC-1 for TRb, these findings suggest that T3 has effects on bone development that are mediated by TRb and independent of GH/IGF-I axis. On the other hand, the inability of GC-1 in completely revert the alterations of bone development suggests that the normal skeleton development require (i) T3 actions mediated by TRa1 and TRb1, or (ii) synergic or additive actions between GH/IGF-I axis and thyroid hormone. To investigate these hypotheses, 21 day-old hypothyroid female rats were treated with T3 or GC-1 in association or not with GH for 4 weeks. Our findings show that T3 interacts with GH to promote body growth, differentiation of growth plate hypertrofic chondrocytes, intramembranous ossification of cranial bone, and increased of bone resistance and other biomechanics parameters that contribute to the best bone quality. On the other hand, ours results suggest strongly that TH acts in bone mass acquisition, in organization of growth plate chondrocytes and endocondral ossification mainly independent of GH/IGF-I axis and via TRa and/or TRb.
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Ferreira, Mari Cassol. "Análise da resposta hormonal pancreática antes e após tratamento com GLP-1 mimético em indivíduos com diabetes tipo 2 portadores da variante rs7903146 do gene TCF7L2." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-01112013-113904/.
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Introdução: O gene TCF7L2 (Transcription Factor 7-Like 2) codifica o fator de transcrição de mesmo nome que, tem importante papel na via Wnt de sinalização intra celular. A via Wnt é constituída por proteínas de integração e ligação dos processos de diferenciação e multiplicação celulares, interagindo com os fatores TCF, e ativando a expressão de genes relacionados ao TCF7L2, sendo este amplamente expresso em vários tecidos. Dados epidemiológicos atuais não deixam dúvidas quanto à forte associação de polimorfismos do gene TCF7L2 com o diabetes tipo 2 (DM2) em diferentes etnias. Apesar de serem pouco conhecidos os mecanismos que envolvem o gene TCF7L2 no DM2, tem sido bem demonstrada a associação do alelo T no rs7903146 com redução da secreção de insulina, redução do efeito das incretinas, principalmente do GLP-1, aumento na secreção de glucagon e a longo prazo, redução da meia vida da célula beta. Em vista destas evidências, aventamos a hipótese de que pacientes com DM2 portadores da variante rs7903146 do gene TCF7L2, ao ser tratados com GLP-1 mimético, poderiam responder de forma peculiar. Objetivos: Avaliar a resposta hormonal pancreática antes e após tratamento com GLP-1 mimético em indivíduos com DM2 portadores da variante rs7903146 do gene TCF7L2. Pacientes e Métodos: Foram genotipados162 indivíduos com DM2 portadores da variante rs7903146 do gene TCF7L2: idade (57,0 ± 7,6) anos, IMC (30,5 ± 5,1) kg/m2. Dessa amostra, 56 pacientes foram divididos em dois grupos conforme o genótipo, sendo 26 CC x 30 CT/TT, e a seguir tratados com Exenatide durante oito semanas. Os testes de refeição foram realizados antes e após o tratamento, para avaliação das concentrações plasmáticas de: Glicose (mg/dl), Insulina (μU/dl), Pró-insulina (pmol/L), Peptideo-c (ng/ml); Glucagon (pg/ml) e GLP-1(pmol/L). Foram comparadas as áreas sob as curvas e os pontos das curvas durante o teste. Análise estatística por ANOVA com dois fatores e medidas repetidas, nível de significância maior que 5%. Resultados: A distribuição genotípica CC x CT x TT foi 41,4% x 47,5% x 11,1% respectivamente. A influência do alelo T na resposta pancreática durante o teste da refeição mostrou que as concentrações plasmáticas de insulina, pró-insulina e peptídeo-c foram maiores no grupo CT/TT do que no CC (p<0,05) mas, não houve diferença na secreção do glucagon, GLP-1 e na glicemia entre os grupos (NS).Com relação à influência do alelo T na resposta ao tratamento verificou-se que o grupo CT/TT apresentou maior redução da secreção de insulina (p<0,005), peptídeo-c (p<0,05) e pró-insulina (p<0,001) do que o grupo CC durante o teste da refeição após o tratamento. Observou-se diminuição da glicemia, do glucagon e do GLP-1 de forma semelhante em ambos os grupos. Além disso, houve diminuição semelhante do peso e da hemoglobina glicosilada em ambos os grupos. Discussão: Os resultados do presente estudo mostraram que a presença do alelo T em indivíduos com DM2 esteve associada à maior secreção de insulina, pró-insulina e peptídeo-c em relação aos não portadores, com semelhantes concentrações séricas de glucagon e glicose em resposta ao teste da refeição. Este dado demonstra que a função da célula β dos portadores da variante rs7903146 apresenta características diferentes dos não portadores. Após o tratamento com Exenatide, os indivíduos com DM2 e genótipo CT/TT, apresentaram valores estatisticamente menores de insulina, pró-insulina e peptídeo-c do que o grupo CC. Os efeitos do GLP-1 na glicemia pós-prandial são atribuídos a mecanismos de supressão do glucagon, lentificação do esvaziamento gástrico e também a efeitos insulinotrópicos e decorrentes de aumento na sensibilidade periférica à insulina. Além disso, já foi demonstrado que o Exenatide aumenta a captação de glicose de forma insulino-independente em músculo esquelético, pelo estímulo dos transportadores de glicose. Portanto, acredita-se que as características da resposta observada após o tratamento nos portadores do alelo T correspondem ao efeito do Exenatide na célula β melhorando o processamento da pró-insulina, peptídeo-c e insulina e ao aumento da captação periférica da glicose. Sugere-se que esse processo seja resultante da melhor interação com os receptores de GLP-1, tanto em fígado, músculo esquelético e pâncreas. Conclusões: Os dados sugerem que indivíduos com DM2 portadores do alelo T no rs7903146 do gene TCF7L2 apresentam mais benefícios do tratamento com Exenatide, pois a secreção de insulina, pró-insulina e peptídeo-c foram condizentes com maior qualidade na função de célula β nesse grupo após o tratamento. Além disso, o presente estudo proporcionou adicionais evidências clínicas de que os problemas que associam o TCF7L2 ao DM2 estão relacionados à tolerância periférica a glicose.Introduction:The TCF7L2 gene (Transcription Factor 7-Like 2) encodes the transcription factor of the same name that has an important role in the intracellular Wnt signaling. The Wnt pathway is composed of connecting and integrating proteins of cell proliferation and differentiation process by interacting with TCF factors, and activating the expression of genes related to TCF7L2, which is widely expressed in several tissues. Current epidemiological data leave no doubt as to the strong association of polymorphisms of the TCF7L2 gene with type 2 diabetes (T2DM) in different ethnic groups. Although they are poorly known mechanisms involving TCF7L2 gene in DM2 the association of the T allele of rs7903146 with reduced insulin secretion, reducing effect of incretins, mainly GLP-1, increase in glucagon secretion and long-term reduction in the half-life of the beta cell, have been well demonstrated. In view of this evidences, we hypothesized that patients with DM2 carriers of the variant rs7903146 of the TCF7L2 gene, being treated with GLP-1 mimetic, could respond in a peculiar way. Objectives: Evaluating the pancreatic hormone response before and after treatment with GLP-1 mimetic in individuals with T2DM carriers of rs7903146 variant of TCF7L2 gene. Patients and Methods: We genotyped 162 individuals with T2DM patients with the variant rs7903146 gene TCF7L2: age ( 57.0 ± 7.6 ) years old, BMI ( 30.5 ± 5.1 ) kg/m2. From this sample, 56 patients were divided into two groups according to the genotype, 26 x 30 CC CT / TT, and then treated with exenatide for eight weeks. Meal tests were conducted before and after treatment to evaluate plasma concentrations of: Glucose ( mg / dl) Insulin ( U / dL ) Proinsulin (pmol / L), C-peptide (ng / ml) , Glucagon (pg / ml) and GLP-1 (pmol / L). The areas under the curves and the points of the curves were compared during the test. Statistical analysis by ANOVA with two factors and repeated measures, significance level greater than 5%. Results: The genotype distribution CC x CT x TT was 41.4% vs. 47.5% vs. 11.1 % respectively. The influence of the T allele in the pancreatic response during the test meal showed that plasma insulin concentrations, pro-insulin and c-peptide were higher in the CT / TT than in CC (p <0.05) but no difference in the glucagon secretion, GLP-1 and glucose in both groups (NS). Regarding to the influence of the T allele in response to treatment has been found that the group CT / TT presented greater reduction in insulin secretion (p <0.005) c-peptide (p <0.05) and proinsulin (p <0.001) than in CC group during the test meal after treatment. There was a decrease in blood glucose, glucagon and GLP-1 similarly in both groups. In addition, there was a similar decrease in weight and glycosylated hemoglobin in both groups. Discussion: The results of this study showed that the presence of the T allele in individuals with T2DM was associated with higher insulin secretion, proinsulin and c-peptide compared to non-carriers, with similar serum concentrations of glucagon and glucose in response to the test meal. This data demonstrates that the function of β cells of carriers of the variant rs7903146 shows different features from non-carriers. After treatment with Exenatide, individuals with T2DM and genotype CT / TT, showed statistically lower values of insulin, proinsulin and c-peptide than the CC group. The effects of GLP-1 on postprandial glycemia mechanisms are attributed to suppression of glucagon, retardation of gastric emptying and also the insulinotropic effects and resulting increase in peripheral sensitivity to insulina. In addition, it was demonstrated that the Exenatide increases glucose uptake independent of insulin in skeletal muscle, the stimulation of glucose transporters way. Therefore, it is believed that the characteristics of the response observed after treatment in patients with the T allele corresponds to the effect of Exenatide in β cell improving the processing of proinsulin, insulin and c-peptide and increasing peripheral glucose uptake. It is suggested that this process is best resulting from the interaction with the GLP-1 receptor in both liver, skeletal muscle and pancreas. Conclusions: These data suggest that individuals with T2DM patients with T allele in rs7903146 of TCF7L2 presents more benefits of treatment with Exenatide, because the secretion of insulin, proinsulin and c-peptide were consistent with higher quality in β cell function in that group after treatment. Moreover, this study provided further evidence that the clinical problems associated with T2DM and TCF7L2 are related to peripheral glucose tolerance.
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Abd, El Aziz Mirna Safia [Verfasser], Juris [Gutachter] Meier, and Horst Harald [Gutachter] Klein. "Metaanalyse von direkten Vergleichsstudien zwischen GLP-1 Rezeptor-Agonisten und Insulin in der Therapie des Typ 2 Diabetes : Unterschied zwischen kurz- und lang-wirksamen Präparaten? / Mirna Safia Abd El Aziz ; Gutachter: Juris Meier, Horst Harald Klein ; Medizinische Fakultät." Bochum : Ruhr-Universität Bochum, 2019. http://d-nb.info/1180028171/34.
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Fetter, Katie L. "Efficacy of Bydureon in Adults with Type 2 Diabetes." UNF Digital Commons, 2014. http://digitalcommons.unf.edu/etd/490.
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Type 2 diabetes is still rapidly on the rise today, affecting 10.5% of individuals in the United States between the ages 45 to 64 and 18.4% of those between the ages of 65 to 74. In the past two decades, type 2 diabetes has doubled in all age groups. Many adults with type 2 diabetes experience difficulty managing their blood sugars, which can result in a range of further complications. One of the newest treatment options on the market today is a glucagon-like peptide-1 (GLP-1) receptor agonist, Bydureon. Similar to Byetta, Bydureon has a main ingredient of exenatide. It offers once a week dosing as opposed to twice-a-day, which may be more appealing to patients.
The purpose of this study was to examine the efficacy of a newly FDA released medication, Bydureon, once weekly dosage in adults with type 2 diabetes. A descriptive, comparative, retrospective study of 35 patients evaluated efficacy by examining Hgb A1C and body mass index in adults with type 2 diabetes at baseline and 3 months after Bydureon was prescribed. Data were collected by a chart review of records in a primary care practice.
Results demonstrated a statistically significant difference between baseline to 3 month means in both Hgb A1C (t (34)= -3.05, p=.0044) and BMI (t (34) = -2.86, p = .0072) for patients using Bydureon.
Health care providers need to individualize the patients’ plans of care to address multifactorial areas of their diabetes care and provide them with an opportunity to successfully meet their goals. Practitioners must be knowledgeable about the treatment options available, including the newer GLP-1 receptor agonist, Bydureon and its efficacy for adults with type 2 diabetes.
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Barbosa, Joana Rafaela Sousa. "Simultaneous administration of insulin and GLP-1 agonists. Technologically possible?" Master's thesis, 2017. http://hdl.handle.net/10316/83770.
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Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaA prática regular de exercício físico juntamente com uma alimentação equilibradasão, nos dias de hoje, fundamentais para a implementação de um estilo de vida saudável, sendo este indispensável quer para a prevenção como para o controlo de várias doenças.A diabetes mellitus, cuja prevalência tem aumentado drasticamente, também obedecea este conjunto de ditas medidas não farmacológicas, como primeiro passo de atuação. No entanto, esta abordagem na maior parte dos casos não é suficiente, sendo necessário um tratamento farmacológico que tem lançado um grande desafio no controlo glicémico devido às limitações das terapêuticas atuais existentes, nomeadamente, o aumento de peso, hipoglicemias e a repetida dependência em injetáveis, contribuindo para a não adesão do paciente.Esta monografia apresenta novas classes e formas farmacêuticas, que têm vindo aultrapassar alguns destes obstáculos e a coadjuvar no tratamento da doença. Adicionalmente à insulina, terapias baseadas no efeito das incretinas, como por exemplo, o exenatido e liraglutido, dispõem cada vez mais de co-formulações com claras vantagens relativamente à monoterapia.As incretinas, hormonas endógenas do nosso organismo, como resultado de váriaspesquisas, demonstraram ter um papel fulcral na homeostase da glucose, chamando aatenção no mundo científico. A mimetização e intensificação da ação das incretinas e da via endógena de secreção da insulina, em terapia combinada, são suscetíveis a apresentar meios fisiologicamente mais relevantes para o controlo metabólico da diabetes tipo 2.O desenvolvimento de sistemas de libertação modificada em formulações orais,mucoadesivas e injeções únicas, minimizam o inconveniente das administrações parentéricas sucessivas. Mais investigações, estudos e práticas clínicas, serão imprescindíveis para compreender as verdadeiras implicações existentes nestas novas opções, os seus perfis de segurança, vantagens e desvantagens, em suma, a sua mais valia na terapia da diabetes.
The regular practice of physical exercise together with a balanced diet, are nowadays,essential for the implementation of a healthy lifestyle, which is indispensable for both, prevention and control, of various diseases.Diabetes mellitus, whose prevalence has increased dramatically, also obeys to this set of non-pharmacological measures, as the first step of action. However, this approach, in most cases is not enough, and it is necessary to implement a pharmacological treatment that has presented a great challenge in glycemic control due to the limitations of existing therapies, such as weight gain, hypoglycemia and repeated reliance on injectable therapies, contributing to patient non-adherence.This monograph presents new classes and pharmaceutical forms, which have beenovercoming some of these obstacles and also help in the treatment of the disease. In addition to insulin, therapies based on incretins effects such as exenatide and liraglutide, increasingly have co-formulations with clear advantages over monotherapy.Incretins, endogenous hormones of our body, as a result of several studies, have been shown to play a central role in glucose homeostasis, drawing attention in the scientific world. The mimicking and enhancement of the action of incretins and of the endogenous insulin secretory pathway, together in combination therapy, are likely to present physiologically more relevant means for the metabolic control of type 2 diabetes.The development of modified release systems in oral, mucoadhesive and singleinjection formulations, minimize the inconvenience of successive parenteral administrations.Further research, studies and clinical practice will be essential to understand the true implications of these new options, their safety profiles, advantages and disadvantages,concisely, their added value in diabetes therapy.
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Cunha, Sara Sofia da Silva. "O Potencial Terapêutico dos Agonistas do GLP-1R na Doença de Alzheimer." Master's thesis, 2018. http://hdl.handle.net/10316/84718.
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Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaA doença de Alzheimer é a doença neurodegenerativa mais comum e é caracterizadapela deterioração progressiva e irreversível das funções cognitivas. As principaiscaraterísticas histopatológicas da doença de Alzheimer compreendem a presença de placasamiloides extracelulares e de emaranhados neurofibrilares intracelulares. Apesar doconhecimento sobre a doença ser cada vez maior, ainda carece de uma terapêutica eficaz ecapaz de reverter ou, até mesmo, retardar a progressão da doença, constituindo assim umdesafio para a investigação científica e ganhando impulso nas últimas décadas.Estudos epidemiológicos sugerem que a diabetes mellitus tipo 2 constitui um fator derisco para o desenvolvimento da doença de Alzheimer, provavelmente devido à disfunção dasinalização da insulina e insulinorresistência nos tecidos cerebrais. Nesta perspetiva, tem sidorecentemente sugerido que medicamentos originalmente desenvolvidos para o tratamentoda diabetes mellitus tipo 2 constituam uma abordagem terapêutica eficiente contra odesenvolvimento da doença de Alzheimer. Um crescente número de estudos pré-clínicossugere que os agonistas do recetor do peptídeo 1 semelhante ao glucagon, como oexenatido, o liraglutido e o lixisenatido, sejam potenciais fármacos terapêuticos na doença deAlzheimer.Assim, a presente monografia pretende substanciar o papel da insulina na doença deAlzheimer e analisar a forma como os mais recentes avanços de um potencial terapêuticoafetam a progressão da patologia da doença de Alzheimer: os agonistas do recetor dopeptídeo 1 semelhante ao glucagon.
Alzheimer’s disease is the most common of progressive disorders and is characterized by progressive and irreversible memory loss and cognitive impairments. The two main histological hallmarks of Alzheimer’s disease include extracellular amyloid plaques and intracellular neurofibrillary tangles. Although the knowledge of the disease is now greater there is still lack of effective therapeutics, able to reverse or even delay the advance of the disease, thus constituting a challenge to the scientific investigation and gaining momentum in the last decades. Epidemiological studies have recently discovered that type 2 diabetes mellitus has been identified as a risk factor for developing Alzheimer’s disease, most likely linked to an impairment of insulin in the brain. In view of the similarities and close association between Alzheimer’s disease and defective brain insulin signalling it has been recently hypothesized that efficient drugs against type 2 diabetes mellitus could be also a beneficial therapeutic strategy against Alzheimer’s disease. There is mounting experimental evidence that glucagon-like peptide-1 receptor agonists, including exenatide, liraglutide, lixisenatide ameliorate show promise as potential drug treatments of Alzheimer’s disease. In the present study the effects of insulin in Alzheimer’s disease are explored as well as how the most recent advances of a potential therapeutics affect the progression of the pathology of this disease: the glucagon-like peptide-1 receptor agonists.
Books on the topic "Insuline – Agonistes"
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Mendosa, David. Losing weight with your diabetes medication: How Byetta and other drugs can help you lose more weight than you ever thought possible. Philadelphia, PA: Da Capo Life Long, 2008.
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Mendosa, David. Losing weight with your diabetes medication: How Byetta and other drugs can help you lose more weight than you ever thought possible. Philadelphia, PA: Da Capo Life Long, 2008.
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(Foreword), Joe Prendergast, ed. Losing Weight with Your Diabetes Medication: How Byetta and Other Drugs Can Help You Lose More Weight than You Ever Thought Possible (Marlowe Diabetes Library). Marlowe & Company, 2008.
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Cropsey, Christopher L., and Patrick B. Knight. Beta Blocker/Calcium Channel Blocker Overdose. Edited by Matthew D. McEvoy and Cory M. Furse. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190226459.003.0088.
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Beta blocker and calcium channel blocker overdose is a rare perioperative complication that manifests with symptoms of altered mental status, hypotension, bradycardia, and cardiovascular collapse. Although the clinical presentation is often similar, the underlying pathophysiology can differ between either cardiogenic or vasodilatory shock. Standard therapies such as calcium administration or beta-adrenergic agonists may be effective but often require much higher doses than normal. The evidence for targeted therapies, such as high-dose insulin infusion and glucagon, is mixed, but these should be considered. Refractory toxicity may require advanced lifesaving measures such as intra-arterial balloon counterpulsation or extracorporeal membrane oxygenation. If prompt cardiovascular support can be achieved, patient outcomes are generally very positive.
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Isbister, Geoffrey, and Colin Page. Management of β-blocker and calcium channel blocker poisoning. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0325.
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β-blocker and calcium channel-blockers can cause life-threatening toxicity due to cardiogenic shock. Both β-blockers and calcium channel-blockers are heterogenous groups of drugs and particular drugs, such as propranolol, diltiazem, and verapamil are far more toxic than the others in their class. The most important investigations in β-blocker and calcium channel-blocker overdose are an electrocardiogram, blood glucose measurement, and electrolytes. Like most overdoses, supportive treatment is the most important, with emphasis on the primary pathophysiology. Early decontamination should be considered based on the severity of the poisoning. Treatment of β-blockers and calcium channel-blockers poisoning, using absolute blood pressure as an endpoint can be misleading and measuring cardiac output can be more informative in gauging response to treatment. There are no specific antidotes, although β-agonists may be effective in β-blocker overdose and calcium has been shown to be effective in calcium channel-blocker overdose. The choice of inotropes and/or vasopressors will differ for β-blockers and calcium channel-blockers. These include isoprenaline, high dose insulin euglycaemia, phosphodiesterase inhibitors, and other catecholaminergic inotropes for β-blocker poisoning and adrenaline, high dose insulin euglycaemia and vasopressors for calcium channel-blocker poisoning.
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Frise, Matthew C., and Jonathan B. Salmon. Disorders of potassium in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0251.
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Plasma potassium levels are maintained in health between 3.5 and 5.0 mmol/L, and reflect total body potassium only in stable states at normal pH. Most true hyperkalaemia results from renal insufficiency. The goals of therapy are myocardial protection and return of plasma potassium to a safe level. Measures are commonly initiated above 5.5 mmol/L; above 6.5 mmol/L, aggressive measures should be adopted and calcium salts given if there are cardiac dysrhythmias or QRS-broadening. Glucose-insulin infusions and beta-2-agonists promote potassium shifts into cells. Diuretics and sodium bicarbonate may be helpful, but persistent hyperkalaemia is an indication for renal replacement therapy. Hypokalaemia may lead to dangerous arrhythmias, skeletal muscle weakness, ileus, and reduced vascular smooth muscle contractility. Rapid replacement should only be undertaken for severe hypokalaemia or in the context of arrhythmias. Once the extracellular deficit is corrected, there will usually be a continuing need for potassium supplementation to replenish intracellular stores.
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Esen, Figen. Disorders of magnesium in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0252.
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Plasma potassium levels are maintained in health between 3.5 and 5.0 mmol/L, and reflect total body potassium only in stable states at normal pH. Most true hyperkalaemia results from renal insufficiency. The goals of therapy are myocardial protection and return of plasma potassium to a safe level. Measures are commonly initiated above 5.5 mmol/L; above 6.5 mmol/L, aggressive measures should be adopted and calcium salts given if there are cardiac dysrhythmias or QRS-broadening. Glucose-insulin infusions and beta-2-agonists promote potassium shifts into cells. Diuretics and sodium bicarbonate may be helpful, but persistent hyperkalaemia is an indication for renal replacement therapy. Hypokalaemia may lead to dangerous arrhythmias, skeletal muscle weakness, ileus, and reduced vascular smooth muscle contractility. Rapid replacement should only be undertaken for severe hypokalaemia or in the context of arrhythmias. Once the extracellular deficit is corrected, there will usually be a continuing need for potassium supplementation to replenish intracellular stores.
Book chapters on the topic "Insuline – Agonistes"
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Loubatières-Mariani, Marie-Madeleine, Pierre Petit, Jeannie Chapal, Dominique Hillaire-Buys, Gyslaine Bertrand, and Gérard Ribes. "Effects of Purinoceptor Agonists on Insulin Secretion." In Adenosine and Adenine Nucleotides: From Molecular Biology to Integrative Physiology, 337–45. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4615-2011-5_38.
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Malaisse-Lagae, F., A. Sener, and W. J. Malaisse. "Stimulation of Insulin Release by Organic Calcium-Agonists." In Advances in Experimental Medicine and Biology, 201–5. Boston, MA: Springer US, 1986. http://dx.doi.org/10.1007/978-1-4684-5314-0_18.
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Richards, Steven. "Thiazolidinedione-Based Insulin Sensitizers:PPAR-γ Agonists for the Treatment of Type 2 Diabetes." In Bioactive Heterocyclic Compound Classes, 327–47. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2013. http://dx.doi.org/10.1002/9783527664450.ch20.
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Long, Harlan B., Rama M. Belagaje, Gerald S. Brooke, Ronald E. Chance, Richard D. DiMarchi, James A. Hoffmann, Steven G. Reams, et al. "A-C-B human proinsulin: A novel insulin agonist and intermediate in the synthesis of human insulin." In Peptides, 93–94. Dordrecht: Springer Netherlands, 1992. http://dx.doi.org/10.1007/978-94-011-2264-1_29.
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Chaouloff, F., V. Baudrie, and D. Laude. "Influence of 5-HT1A and 5-HT2 Receptor Agonists on Blood Glucose and Insulin Levels." In Serotonin: Molecular Biology, Receptors and Functional Effects, 339–45. Basel: Birkhäuser Basel, 1991. http://dx.doi.org/10.1007/978-3-0348-7259-1_32.
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Chlup, Rudolf, Richard Kaňa, Lada Hanáčková, Hana Zálešáková, and Blanka Doubravová. "Pathophysiologic Approach to Type 2 Diabetes Management: One Centre Experience 1980–2020." In Type 2 Diabetes [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.96237.
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This overview summarizes the evolution of pathophysiologic treatment of diabetes type 2 (T2D) in the period of the last 40 years. Randomized Controlled Trials (RCT) and Real World Evidence (RWE) studies resulted in recent Statements of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) in the year 2020. Case reports and studies of a single-centre in Czech Republic are reported. The authors demonstrate the impact of (1) multiple doses of rapid insulin, (2) multiple doses of rapid or ultrarapid insulin analogs (3) continuous subcutaneous insulin infusion (CSII) (4) incretin receptor agonists, (5) fixed combination of insulin degludec with liraglutide (IDegLira) and (6) SGLT2 inhibitor dapagliflozin, on plasma glucose concentration, HbA1c, body mass and patient satisfaction. The importance of therapeutic patients´ education and technology (personal glucometers, continuous/flash glucose monitors, insulin pens/pumps) is emphasized. Most of the observations were already published. Hence, individually adopted education, lifstyle, technical equipment, incretin receptor agonists and/or metformin and/or gliflozins and/or insulin analogs appear to be the core of an effective pathophysiologic approach. Scientific conclusions from RCTs, RWE trials and own clinical case reports may prevail over clinical inertia and induce early implementation of effective methods into routine T2D treatment.
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Shah, Unmesh, and Timothy J. Kowalski. "GPR119 Agonists for the Potential Treatment of Type 2 Diabetes and Related Metabolic Disorders." In Incretins and Insulin Secretion, 415–48. Elsevier, 2010. http://dx.doi.org/10.1016/b978-0-12-381517-0.00016-3.
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Li, Jie Jack. "Sitagliptin (Januvia)." In Top Drugs. Oxford University Press, 2015. http://dx.doi.org/10.1093/oso/9780199362585.003.0012.
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Diabetes has been known since antiquity. In fact, the term “diabetes mellitus” comes from the Greek meaning “siphon and honey” due to the excess excretion (siphon or faucet) of hyperglycemic (sweetened, or honeyed) urine associated with diabetes. In ancient times, diabetes was mostly type I, which usually manifests acutely in the young, secondary to certain underlying insults (possibly infections) to the islet cells of the pancreas resulting in an absolute lack of insulin. Insulin was discovered by Banting and Best in 1921, and insulin injection has literally saved millions of lives since then. With the wondrous efficacy that insulin bestows, type I diabetes is largely controlled because type I diabetes is insulindependent. However, type II diabetes, a more prevalent form of diabetes, is not insulin-dependent. In ancient times, when nutrition was scarce and obesity was not prevalent, type II diabetes mellitus (T2DM) was extremely rare. Indeed, type II diabetes is a disease more frequently associated with maturity, obesity, and gradually increasing blood glucose concentrations, and it may be asymptomatic for some time, only discovered on routine glucose screening. In fact, with the increasing body weight of the general population of the developed world, type II diabetes is becoming an epidemic. Serious complications of diabetes include nephropathy (kidney diseases), neuropathy (nerve damage), and retinopathy (blindness). Diabetes is the most common cause of blindness and amputation in the elderly in the United States. Oral diabetes drugs are required for most type II diabetic patients. Diabetes drugs may be classified into four categories: (a) agents that augment the supply of insulin such as sulfonylureas; (b) agents that enhance the effectiveness of insulin such as biguanides and thiazolidinediones; (c) GLP agonists; and (d) DPP4 Inhibitors. The efficacy of all the antidiabetic drugs can be monitored by measuring glycosylated hemoglobin (HaA1c) as a long term marker of elevated blood glucose. The amount of HaA1c reflects the average level over the last 120 days, the life span of a red blood cell, and should remain below 7%.
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Coughlan, Kimberly, Juli Jones, David Kubasiak, Tiffany Gareski, Thaddeus J. Unger, Sarah Will, Ariful Qadri, Xiangping Li, and Mylene Perreault. "GLP1 Receptor Agonists Reduce Food Intake While Differentially Activating Neurons in the Hypothalamus and Hindbrain." In BASIC/TRANSLATIONAL - Insulin Action & Gut Hormones, P1–480—P1–480. The Endocrine Society, 2011. http://dx.doi.org/10.1210/endo-meetings.2011.part2.p8.p1-480.
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Manov, Andrey Emanuilov, Ashan Thomas Hatharasinghe, and Katrina Equinox Lopez. "Comparison of the effect on Hyperglycemia and the Adverse Effects among Different GLP-1 Receptor Agonists Added to Basal Insulin and between GLP-1 Receptor Agonists and Basal Insulin Versus Basal-Plus or Basal-Bolus Insulin in Type 2 Diabetes: A Meta-Analysis." In New Frontiers in Medicine and Medical Research Vol. 10, 147–63. Book Publisher International (a part of SCIENCEDOMAIN International), 2021. http://dx.doi.org/10.9734/bpi/nfmmr/v10/4105f.
Full textConference papers on the topic "Insuline – Agonistes"
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Nie, Zhenying, Becky Proskocil, David Jacoby, and Allison Fryer. "Potentiation effect of insulin on M3 muscarinic receptor agonist induced airway smooth muscle contraction." In ERS International Congress 2019 abstracts. European Respiratory Society, 2019. http://dx.doi.org/10.1183/13993003.congress-2019.pa4207.
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Zhang, Xihong, Sidhant Varma, and Douglas Yee. "Abstract 4406: Inducible knockdown of insulin receptor substrate I desensitizes ER alpha response to both agonist (estradiol) and antagonist (fulvestrant) in MCF-7L breast cancer cells." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-4406.
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