Academic literature on the topic 'Animals Hypoglycemia'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Animals Hypoglycemia.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "Animals Hypoglycemia"
1
Ichord, R. N., F. J. Northington, D. van Wylen, M. V. Johnston, C. Kwon, and R. J. Traystman. "Brain O2 consumption and glutamate release during hypoglycemic coma in piglets are temperature sensitive." American Journal of Physiology-Heart and Circulatory Physiology 276, no. 6 (June 1, 1999): H2053—H2062. http://dx.doi.org/10.1152/ajpheart.1999.276.6.h2053.
Full textAbstract:
Hypoglycemic injury in the mature brain is mediated by excitotoxicity, which is worsened by disordered cellular energy metabolism. The role of excitotoxicity in relation to brain energy metabolism during hypoglycemia has not been studied in the immature brain. Brain oxygen consumption ([Formula: see text]) increases during hypoglycemia in piglets, whereas [Formula: see text] decreases in adult pig models. We tested the hypothesis that increased[Formula: see text] during hypoglycemic coma is temperature dependent and coincides with increased excitatory amino acids (EAA). We measured cerebral blood flow (CBF),[Formula: see text], and cortical microdiaysate EAA in pentobarbital-anesthetized piglets during hypoglycemic coma and during 2 h of recovery and in normoglycemic controls. In warmed animals brain temperature was kept normothermic (38.5°C). In unwarmed animals brain temperature was allowed to fall (37.6°C). During hypoglycemia CBF increased similarly in warmed animals and unwarmed animals;[Formula: see text] increased in warmed animals but not unwarmed animals. Glutamate increased during coma and increased more in warmed animals than unwarmed animals but normalized quickly during recovery. EEG recovered earlier in unwarmed animals. We conclude that during a hypoglycemic coma in the immature brain,[Formula: see text] and glutamate are increased in a temperature-dependent manner.
2
Kim, Young-Baeg, Jeffrey M. Gidday, Ernesto R. Gonzales, Aarti R. Shah, and T. S. Park. "Effect of hypoglycemia on postischemic cortical blood flow, hypercapnic reactivity, and interstitial adenosine concentration." Journal of Neurosurgery 81, no. 6 (December 1994): 877–84. http://dx.doi.org/10.3171/jns.1994.81.6.0877.
Full textAbstract:
✓ Hypoglycemia increases the vulnerability of the perinatal brain to asphyxia, but it is not known if hypoglycemia-induced changes in cerebral hemodynamics and vascular reactivity underlie this vulnerability. This study tested the hypothesis that hypoglycemia exacerbates postischemic hypoperfusion, and impairs postischemic CO2 reactivity. The authors also examined the hypothesis that postischemic hypoperfusion is associated with a reduction in the interstitial concentration of the vasodilator metabolite adenosine. Global cerebral ischemia of 10 minutes duration was induced in newborn pigs anesthetized with isoflurane by occlusion of subclavian and brachiocephalic arteries; cortical cerebral blood flow (CBF) and interstitial adenosine concentration were evaluated simultaneously using the combined hydrogen clearance/microdialysis technique. Hypoglycemia (blood glucose < 25 mg/dl) was induced by regular insulin (25 IU/kg) administered intravenously 2 hours prior to induction of ischemia. In the eight normoglycemic animals, baseline CBF was 38 ± 4 ml/min/100 gm and baseline adenosine concentration was 1.2 ± 0.1 µM; in the eight hypoglycemic animals, these values were 39% (p < 0.05) and 62% (p < 0.05) greater, respectively, under baseline conditions. At 1 hour of postischemic reperfusion in normoglycemic animals, CBF was reduced 39% relative to the preischemic baseline (p < 0.01), concomitant with a 27% reduction (p < 0.05) in adenosine concentration, suggesting that this lowered concentration may underlie delayed hypoperfusion. These postischemic reductions in CBF and interstitial adenosine concentration were significantly greater in hypoglycemic animals, with CBF and adenosine concentration reduced 70% (p < 0.001) and 71% (p < 0.01), respectively, relative to baseline. In nine animals preischemic reactivity to hypercapnia was unaffected by hypoglycemia. Postischemic hypercapnic reactivity was retained in the eight normoglycemic animals, but was attenuated 73% (p < 0.05) in hypoglycemic animals. Thus, in the newborn pig, hypoglycemia exacerbates postischemic cortical hypoperfusion and impairs postischemic cerebrovascular reactivity to hypercapnia.
3
LaGamma, Edmund F., Necla Kirtok, Owen Chan, and Bistra B. Nankova. "Partial blockade of nicotinic acetylcholine receptors improves the counterregulatory response to hypoglycemia in recurrently hypoglycemic rats." American Journal of Physiology-Endocrinology and Metabolism 307, no. 7 (October 1, 2014): E580—E588. http://dx.doi.org/10.1152/ajpendo.00237.2014.
Full textAbstract:
Recurrent exposure to hypoglycemia can impair the normal counterregulatory hormonal responses that guard against hypoglycemia, leading to hypoglycemia unawareness. This pathological condition known as hypoglycemia-associated autonomic failure (HAAF) is the main adverse consequence that prevents individuals with type 1 diabetes mellitus from attaining the long-term health benefits of tight glycemic control. The underlying molecular mechanisms responsible for the progressive loss of the epinephrine response to subsequent bouts of hypoglycemia, a hallmark sign of HAAF, are largely unknown. Normally, hypoglycemia triggers both the release and biosynthesis of epinephrine through activation of nicotinic acetylcholine receptors (nAChR) on the adrenal glands. We hypothesize that excessive cholinergic stimulation may contribute to impaired counterregulation. Here, we tested whether administration of the nAChR partial agonist cytisine to reduce postganglionic synaptic activity can preserve the counterregulatory hormone responses in an animal model of HAAF. Compared with nicotine, cytisine has limited efficacy to activate nAChRs and stimulate epinephrine release and synthesis. We evaluated adrenal catecholamine production and secretion in nondiabetic rats subjected to two daily episodes of hypoglycemia for 3 days, followed by a hyperinsulinemic hypoglycemic clamp on day 4. Recurrent hypoglycemia decreased epinephrine responses, and this was associated with suppressed TH mRNA induction (a measure of adrenal catecholamine synthetic capacity). Treatment with cytisine improved glucagon responses as well as epinephrine release and production in recurrently hypoglycemic animals. These data suggest that pharmacological manipulation of ganglionic nAChRs may be promising as a translational adjunctive therapy to avoid HAAF in type 1 diabetes mellitus.
4
Semick, Danielle N., Stephanie L. Shaver, Heather N. Cornell, Nancy C. Bradley, and Rachael E. Kreisler. "Perioperative blood glucose concentrations in kittens following overnight fasting and gonadectomy." Journal of Feline Medicine and Surgery 20, no. 4 (May 30, 2017): 344–48. http://dx.doi.org/10.1177/1098612x17710590.
Full textAbstract:
Objectives The objective of this study was to determine if hypoglycemia is an effect of overnight fasting and gonadectomy in kittens, as well as to determine predictors of baseline and postoperative blood glucose. Methods This was a prospective observational study. Seventy-five kittens between the age of 8 and 16 weeks undergoing routine castration or ovariohysterectomy at an animal shelter were included. Two blood glucose measurements were analyzed per kitten after an overnight fast: a baseline reading prior to preoperative examination, and a reading immediately postoperatively. Predictors of the baseline and postoperative blood glucose levels were determined using multi-level mixed-effects linear regression. Results Kittens, when fasted overnight, were not hypoglycemic (<60 mg/dl). No kittens exhibited clinical signs consistent with hypoglycemia. No kittens had a blood glucose <70 mg/dl postoperatively. Postoperative hyperglycemia (>150 mg/dl) was observed in 44% of kittens. The only predictor of fasted blood glucose levels was body condition score. The only predictor of postoperative blood glucose levels was the fasting blood glucose value. Conclusions and relevance Overnight fasting prior to elective sterilization in 8- to 16-week-old kittens did not result in hypoglycemia. Concern regarding hypoglycemia after a prolonged fast in kittens may be unwarranted for short procedures in healthy animals.
5
Kim, Mina, Zhao-Xue Yu, Bertil B. Fredholm, and Scott A. Rivkees. "Susceptibility of the developing brain to acute hypoglycemia involving A1 adenosine receptor activation." American Journal of Physiology-Endocrinology and Metabolism 289, no. 4 (October 2005): E562—E569. http://dx.doi.org/10.1152/ajpendo.00112.2005.
Full textAbstract:
It has been suggested that the developing brain is less vulnerable to the adverse effects of hypoglycemia than the mature brain; however, this issue remains controversial. We also do not know the magnitude or duration of hypoglycemia needed to trigger hypoglycemic brain injury during development. To address this issue a series of in vivo and in vitro studies were performed. First, we established an acute model of insulin-induced hypoglycemia in mice by administering 3 U/kg of neutral-protamine Hagadorn insulin subcutaneously. When we examined degenerating neurons in hippocampus and striatum by TUNEL labeling, injury was observed after 4 h of hypoglycemia in postnatal day ( P)7 mice, and we observed more cell injury in animals rendered hypoglycemic at P 7 than at P21. Studies of hippocampal slice cultures revealed that reduction in glucose concentration induced more neuronal injury in slices prepared from P3 and P7 than from P14 and P21 mice. Treatment of slices with an adenosine A1 receptor (A1AR) antagonist reduced the hypoglycemic damage, whereas agonists increased damage, particularly in slices prepared from very young pups. This suggests a critically important role for A1ARs, which was further demonstrated by the reduction of hypoglycemic damage in hippocampal slices prepared from A1AR−/− mice. Furthermore, insulin-induced hypoglycemia in P7 A1AR−/− mice did not increase TUNEL-positive cells, but a major increase was seen in A1AR+/− mice. These observations show that the developing nervous system is indeed sensitive to acute hypoglycemic injury and that A1AR activation contributes to damage induced by hypoglycemia, particularly in immature mouse brain.
6
Kaya, Mehmet, Mutlu Küçük, Rivaze Bulut Kalayci, Vedat Cimen, Candan Gürses, Imdat Elmas, and Nadir Arican. "Magnesium sulfate attenuates increased blood-brain barrier permeability during insulin-induced hypoglycemia in rats." Canadian Journal of Physiology and Pharmacology 79, no. 9 (September 1, 2001): 793–98. http://dx.doi.org/10.1139/y01-046.
Full textAbstract:
Magnesium probably protects brain tissue against the effects of cerebral ischemia, brain injury and stroke through its actions as a calcium antagonist and inhibitor of excitatory amino acids. The effects of magnesium sulfate on cerebrovascular permeability to a dye, Evans blue, were studied during insulin-induced hypoglycemia with hypothermia in rats. Hypoglycemia was induced by an intramuscular injection of insulin. After giving insulin, each animal received MgSO4 (270 mg/kg) ip, followed by a 27 mg/kg dose every 20 min for 2.5 h. Plasma glucose and Mg2+ levels of animals were measured. Magnesium concentrations increased in the serum following MgSO4 administration (6.05 ± 0.57 vs. 2.58 ± 0.14 mg/dL in the Mg2+ group, and 7.14 ± 0.42 vs. 2.78 ± 0.06 mg/dL in the insulin + Mg2+ group, P < 0.01). Plasma glucose levels decreased following hypoglycemia (4 ± 0.66 vs. 118 ± 2.23 mg/dL in the insulin group, and 7 ± 1.59 vs. 118 ± 4.84 mg/dL in the insulin + Mg2+ group, P < 0.01). Blood-brain barrier permeability to Evans blue considerably increased in hypoglycemic rats (P < 0.01). In contrast, blood-brain barrier permeability to Evans blue was significantly reduced in treatment of hypoglycemic rats with MgSO4 (P < 0.01). These results indicate that Mg2+ greatly reduced the passage of exogenous vascular tracer bound to albumin into the brain during hypoglycemia with hypothermia. Mg2+ could have protective effects on blood-brain barrier permeability against insulin-induced hypoglycemia.Key words: blood-brain barrier, hypoglycemia, Mg2+, Evans-blue.
7
Dessouky, Arigue A., Zienab A. Gouda, Mona A. A. Arafa, Yaser H. A. Elewa, Amany M. Abo-Ouf, and Eman M. Askar. "Hypoxia-Preconditioned Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Mitigate Hypoglycemic Testicular Injury Induced by Insulin in Rats." Cells Tissues Organs 209, no. 2–3 (2020): 83–100. http://dx.doi.org/10.1159/000510363.
Full textAbstract:
Hypoglycemia is a neglected metabolic disorder. Thus, we evaluated the protective effect of hypoxia-preconditioned human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) on hypoglycemic testicular injury. We examined 56 testes from 28 animals: 7 rats with insulin-induced hypoglycemia (HG group), 7 hypoglycemic rats which received an intratesticular injection of hUCB-MSCs (HG-MSC group), and 14 untreated control rats. Testosterone level, testicular catalase (CAT) activity, and malondialdehyde (MDA) level were analyzed. Immunostaining for specific testicular germ and somatic cell markers was performed. Proliferating and apoptotic cells were detected by anti-PCNA and anti-caspase-3, respectively. Morphometrical data were statistically analyzed. The hypoglycemic rats showed a significant decrease in testosterone level and CAT activity and a significant increase in MDA production. Examination of histological structure and protein expression of diverse germ cell markers revealed collapsed tubules that were lined by degenerated germ cells, decreased lactate dehydrogenase type C immune expression, as well as decreased proliferating and increased apoptotic cells number in hypoglycemic testes. Injection of MSCs improved testicular biochemical parameters, preserved germ cells and somatic cells, and decreased apoptosis. In conclusion, hypoxia-preconditioned hUCB-MSCs attenuate rat testicular injury caused by insulin-induced hypoglycemia. Avoidance and rapid management of hypoglycemia are necessary to avoid significant testicular injury.
8
Sieber, F. E., R. C. Koehler, S. A. Derrer, C. D. Saudek, and R. J. Traystman. "Hypoglycemia and cerebral autoregulation in anesthetized dogs." American Journal of Physiology-Heart and Circulatory Physiology 258, no. 6 (June 1, 1990): H1714—H1721. http://dx.doi.org/10.1152/ajpheart.1990.258.6.h1714.
Full textAbstract:
We examined the effects of moderate hypoglycemia with near-normal cerebral glucose consumption on cerebral autoregulation during graded hemorrhagic hypotension in anesthetized dogs. Four groups of animals (n = 8 each) were studied: normoglycemia, insulin-induced hypoglycemia (1.1 mM), normoglycemia plus alpha- and beta-adrenergic blockade [propranolol (1 mg/kg loading dose + 1 mg.kg-1.h-1 infusion) plus phentolamine (2 mg/kg loading dose + 2 mg/min infusion)], and hypoglycemia plus alpha- and beta-adrenergic blockade. As cerebral perfusion pressure was reduced to 40-50 mmHg, cerebral blood flow and O2 consumption increased in the hypoglycemic group. These increases were not observed after adrenergic blockade or in the normoglycemic groups. The perfusion pressure at which cerebrovascular resistance was minimal was higher during hypoglycemia (40 mmHg) and hypoglycemia plus blockade (50 mmHg) than in either of the normoglycemic groups (30 mmHg). This study demonstrates that hypoglycemia increases the lower limit of cerebral autoregulation during hypotension. Furthermore, adrenergic mechanisms acting during combined hypoglycemia and hemorrhagic hypotension increase cerebral blood flow and O2 consumption and attenuate the hypoglycemia-induced increase in the lower limit of autoregulation.
9
Fujita, Satoshi, MaryAnn Bohland, Graciela Sanchez-Watts, Alan G. Watts, and Casey M. Donovan. "Hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons." American Journal of Physiology-Endocrinology and Metabolism 293, no. 1 (July 2007): E96—E101. http://dx.doi.org/10.1152/ajpendo.00415.2006.
Full textAbstract:
To elucidate the type of spinal afferent involved in hypoglycemic detection at the portal vein, we considered the potential role of capsaicin-sensitive primary sensory neurons. Specifically, we examined the effect of capsaicin-induced ablation of portal vein afferents on the sympathoadrenal response to hypoglycemia. Under anesthesia, the portal vein was isolated in rats and either capsaicin (CAP) or the vehicle (CON) solution applied topically. During the same surgery, the carotid artery (sampling) and jugular vein (infusion) were cannulated. One week later, all animals underwent a hyperinsulinemic hypoglycemic clamp, with glucose (variable) and insulin (25 mU·kg−1·min−1) infused via the jugular vein. Systemic hypoglycemia (2.76 ± 0.05 mM) was induced by minute 75 and sustained until minute 105. By design, no significant differences were observed in arterial glucose or insulin concentrations between groups. When hypoglycemia was induced in CON, the plasma epinephrine concentration increased from 0.67 ± 0.05 nM at basal to 36.15 ± 2.32 nM by minute 105. Compared with CON, CAP animals demonstrated an 80% suppression in epinephrine levels by minute 105, 7.11 ± 0.55 nM ( P < 0.001). A similar response to hypoglycemia was observed for norepinephrine, with CAP values suppressed by 48% compared with CON. Immunohistochemical analysis of the portal vein revealed an 85% decrease in the number of calcitonin gene-related peptide-reactive nerve fibers following capsaicin-induced ablation. That the suppression in the sympathoadrenal response was comparable to our previous findings for total denervation of the portal vein indicates that hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons.
10
Ionut, Viorica, Ana Valeria B. Castro, Orison O. Woolcott, Darko Stefanovski, Malini S. Iyer, Josiane L. Broussard, Hasmik Mkrtchyan, et al. "Essentiality of Portal Vein Receptors in Hypoglycemic Counterregulation: Direct Proof Via Denervation in Male Canines." Endocrinology 155, no. 4 (April 1, 2014): 1247–54. http://dx.doi.org/10.1210/en.2013-1794.
Full textAbstract:
A major issue of in the treatment of diabetes is the risk of hypoglycemia. Hypoglycemia is detected both centrally and peripherally in the porto-hepatic area. The portal locus for hypoglycemic detection was originally described using the “local irrigation of the liver” approach in a canine model. Further work using portal vein denervation (DEN) in a rodent model characterized portal hypoglycemic sensing in detail. However, recent controversy about the relevance of rodent findings to large animals and humans prompted us to investigate the effect of portal DEN on the hypoglycemic response in the canine, a species with multiple similarities to human glucose homeostasis. Hypoglycemic hyperinsulinemic clamps were performed in male canines, before (PRE) and after (POST) portal vein DEN or sham surgery (CON, control). Insulin (30 pmol/kg·min) and glucose (variable) were infused to slowly decrease systemic glycemia to 50 mg/dL over 160 minutes. The average plasma glucose during clamp steady state was: 2.9 ± 0.1 mmol DEN-PRE, 2.9 ± 0.2 mmol DEN-POST, 2.9 ± 0.1 mmol CON-PRE, and 2.8 ± 0.0 mmol CON-POST. There were no significant differences in plasma insulin between DEN and CON, PRE and POST experiments. The epinephrine response to hypoglycemia was reduced by 62% in DEN but not in CON. Steady-state cortisol was 46% lower after DEN but not after CON. Our study shows, in a large animal model, that surgical disconnection of the portal vein from the afferent pathway of the hypoglycemic counterregulatory circuitry results in a substantial suppression of the epinephrine response and a significant impact on cortisol response. These findings directly demonstrate an essential role for the portal vein in sensing hypoglycemia and relating glycemic information to the central nervous system.
Dissertations / Theses on the topic "Animals Hypoglycemia"
1
Rabelo, Alana Fonteles Lima. "Estudo da toxicidade hepÃtica da trans-desidrocrotonina (t-dctn), um diterpeno obtido de Croton Cajucara Benth, e de estratÃgias farmacolÃgicas preventivas em modelos animais." Universidade Federal do CearÃ, 2008. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=2898.
Full textAbstract:
Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgicoA trans-desidrocrotonina (t-DCTN) Ã o principal composto diterpenÃide presente no extrato da casca do caule de Croton cajucara (Euphorbiaceae). Este diterpeno possui um amplo espectro de atividades farmacolÃgicas que inclui antiinflamatÃria, antinociceptiva, e efeitos hipoglicemiante e hipolipidÃmico. SubstÃncias com esse perfil farmacolÃgico sÃo comumente associadas a efeitos deletÃrios sobre o fÃgado. Tendo em vista que estudos in vitro e in vivo mostraram uma hepatotoxicidade da t-DCTN, o presente estudo objetivou analisar em maior profundidade o seu potencial em causar dano hepÃtico e, entÃo, buscar estratÃgias farmacolÃgicas para mitigar tal toxicidade. Desta forma, os experimentos iniciais foram direcionados para observaÃÃo do dano hepÃtico em camundongos que receberam, por gavagem, uma Ãnica (aguda) ou repetidas administraÃÃes de t-DCTN, em doses que variam de 10 a 300 mg/kg. A segunda sÃrie de experiÃncias foi projetada para avaliar os efeitos do (i) prÃ-condicionamento com a menor dose de t-DCTN (10 mg/kg) ou etanol (1 g/kg), e do (ii) prÃ-tratamento com Vitamina E ou N-acetilcisteÃna (NAC) no dano hepÃtico associado a altas doses de t-DCTN em camundongos. Um possÃvel envolvimento de NO tambÃm foi verificado no efeito prÃ-condicionante de t-DCTN e/ou Etanol. t-DCTN em doses mais altas (100 e 300 mg/kg, v.o.) causou dano hepÃtico severo, comprovado por aumentos significativos (p <0,001) nos nÃveis sÃricos de ALT e AST e por alteraÃÃes histopatolÃgicas, quando administrada isolada ou repetidamente. Em contraste, as doses de 10 e 30 mg/kg nÃo promoveram alteraÃÃes significantes, sugerindo que a toxicidade da t-DCTN Ã dose dependente. O prÃ-condicionamento farmacolÃgico com t-DCTN (10 mg/kg, v.o.) e Etanol (1 g/kg, v.o.) atenuaram significativamente (p <0,001) a hepatotoxicidade associada a alta dose (100 mg/kg) de t-DCTN, como comprovado pela reduÃÃo na atividade das transaminases sÃricas, como tambÃm nas lesÃes hepÃticas. A suplementaÃÃo em camundongos com L-arginina, um substrato para geraÃÃo de NO, preveniu parcialmente o efeito hepatotÃxico da t-DCTN, possivelmente devido a um aumento na microcirculaÃÃo hepÃtica. Adicionalmente, o prÃ-tratamento com Vitamina E, mas nÃo com NAC, reduziu efetivamente os efeitos hepatotÃxicos de t-DCTN, comprovado pela diminuiÃÃo dos nÃveis sÃricos de ALT e AST, de TBARS hepÃtico e das alteraÃÃes histolÃgicas. Isto sugere que Vitamina E protege contra o aumento da peroxidaÃÃo lipÃdica hepÃtica promovido por alta dose de t-DCTN. Paradoxalmente, comparada a outros hepatotoxicantes relatados na literatura, a t-DCTN aumenta os nÃveis de glutationa hepÃtica que pode ser uma conseqÃÃncia do estresse oxidativo prolongado. Em conjunto, estes resultados confirmam as observaÃÃes anteriores sobre o potencial hepatotÃxico da t-DCTN e sugerem que um aumento no estresse oxidativo e na peroxidaÃÃo lipÃdica das membranas dos hepatÃcitos contribui para o dano hepÃtico desse diterpeno. A suplementaÃÃo com Vitamina E, um antioxidante lipossolÃvel, ou o prÃ-condicionamento com doses menores de t-DCTN ou etanol poderiam ser profilaticamente Ãtil para superar os efeitos hepatotÃxicos de t-DCTN
The trans-dehydrocrotonin (t-DCTN) is a major diterpenoid compound present in bark extracts of Croton cajucara (Euphorbiaceae) stem. This diterpene possesses a wide spectrum of pharmacological activity that include anti-inflammatory, antinociceptive, hypoglycemic and antihyperlipidemic effects. Deleterious effects on liver are not uncommon with substances having this pharmacological profile. Keeping in view the reported hepatotoxicity of t-DCTN in vitro and in vivo, the present study was carried out to analyse in greater depth its potential to cause hepatic damage and then to seek pharmacological strategies to mitigate such a toxicity. Accordingly, our initial experiments were aimed to observe the hepatic damage in mice that received the single (acute) or repeated administrations of t-DCTN by oral gavage, at doses ranging from 10 to 300 mg/kg. The second series of experiments were designed to evaluate the effects of (i) pre-conditioning with a smaller dose t-DCTN or ethanol, and (ii) pre-treatments with Vitamin E or NAC on high-dose -associated hepatic injury in mice. A possible involvement of NO was also verified on the pre-conditioning effects of t-DCTN and or Ethanol. t-DCTN at higher doses (100 e 300 mg/kg, v.o.) caused severe hepatic damage as evidenced by significant (p<0,001) increases in the serum levels of ALT and AST and histopathological alterations, whether administered singly or repeatedly. In contrast, at the doses of 10 e 30 mg/kg, there were no significant alterations suggesting that the toxicity is a dose-related one. Pharmacological pre-conditioning with t-DCTN (10 mg/kg, p.o.) e Ethanol (1 g/kg, p.o.) significantly (p<0,001) attenuated the high-dose t-DCTN (100 mg/kg) -associated hepatotoxicity, as evidenced by reductions in serum enzyme activities as well as the hepatic lesions. In mice supplemented with L-arginine, the substrate for NO generation only partially prevented the hepatotoxic effect of t-DCTN most possibly due to an improved hepatic microcirculation. Additionally, pre-treatment with Vitamin E but not the NAC effectively reduced hepatotoxic effect of t-DCTN, evidenced by diminished serum levels of ALT, AST and hepatic TBARS and histological alterations. This suggests that Vitamine E protects against the increased hepatic lipid peroxidation promoted by high-dose t-DCTN. Paradoxically, compared to other hepatotoxicants reported in literature, t-DCTN enhanced the hepatic glutathione levels, which may be a consequence of prolonged oxidative stress. Taken together, these results confirm the earlier observations on the hepatotoxic potential of t-DCTN and suggest that an increased oxidative stress and lipid peroxidation of hepatocyte membranes contributes to hepatic damage. Supplementation with liposoluble antioxidant Vitamina E, or prÃ-conditioning with smaller doses of t-DCTN or ethanol might be useful prophylactically to overcome hepatotoxic effects of t-DCTN
2
Henriques, Nathalia Aparecida de Paula Camaforte [UNESP]. "Avaliação da atividade hipoglicemiante do extrato bruto de Bauhinia holophylla (Steud.) em camundongos diabéticos induzidos por estreptozotocina." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/108524.
Full textAbstract:
Made available in DSpace on 2014-08-13T14:50:42Z (GMT). No. of bitstreams: 0
Previous issue date: 2013-07-30Bitstream added on 2014-08-13T18:00:56Z : No. of bitstreams: 1
000750041.pdf: 2177704 bytes, checksum: 3b2c1f34dc67cf43d4c50a885f043499 (MD5)O termo Diabetes mellitus (DM) descreve uma desordem metabólica caracterizada por hiperglicemia crônica que leva a alterações no metabolismo de carboidratos, lipídeos e proteínas resultante de defeitos na ação, secreção de insulina, ou ambos. Tais alterações levam a sérias consequências no individuo diabético, como perda de peso, aumento dos níveis de lipídeos no sangue podendo levar ao aumento da incidência de doenças cardiovasculares como aterosclerose e infarto. Além disso, pode causar doenças renais e danos à visão, e em casos mais graves, óbito. A incidência de pessoas diabéticas tem aumentado a cada ano, e pesquisas realizadas recentemente apontam que esse é um número que só tende a aumentar nos próximos anos, principalmente devido aos péssimos hábitos alimentares e estilo de vida sedentário. O tratamento para o DM inclui insulinoterapia e o uso de hipoglicemiantes orais. No entanto, sabe-se que esses medicamentos possuem efeitos adversos, como ganho de peso, desconfortos abdominais e diarreias. Partindo dessas informações, a busca de novas alternativas para o tratamento de DM tem crescido muito nos últimos anos. O uso de plantas medicinais no tratamento de diversas doenças, como o diabetes, é feito desde os primórdios da humanidade. Diante disso, a pesquisa envolvendo plantas medicinais com propriedades hipoglicemiantes tem sido alvo dos pesquisadores nos últimos anos, principalmente para comprovação da sua eficácia e verificação da toxicidade das mesmas. A família Fabaceae possui aproximadamente 300 espécies, popularmente conhecidas como pata-de-vaca ou unhade- boi, devido ao formato de suas folhas e são amplamente utilizadas como analgésicos, antiinflamatórios e no tratamento de diabetes. O gênero Bauhinia, pertencente a essa família possui muitas espécies que são utilizadas no tratamento do diabetes. Diante disso, o objetivo desse trabalho foi avaliar a atividade hipoglicemiante do ...
The term Diabetes mellitus (DM) defines a metabolic disorder characterized by cnronic hyperglycemia, which leads to alterations in carbohydrate, proteins and lipids metabolism resultant of defects in insulin action andJor secretion. Those alterations lead to serious consequences to diabetic people as weight loss, increase incidence of cardiovascular diseases, renal and optical diseases, and in some cases, death. The incidence of diabetic people is increasing every year and recent1y researches showed that this number will increase on next years, mainly due to bad eating habits and sedentary life style. The treatment of DM inc1udes insulin therapy and the use of oral hypoglycemic agents. However, those medicaments have many collateral effects as weight gain, abdominal discomforts and diarrheas. Based on this information, studies involving new altematives for the treatment of DM are growing in the last years. The use of medicinal plants in the treatment of diverse diseases like diabetes has been done since the beginning of humanity. Due to this, the studies involving medicinal plants with hypoglycemic properties have been the target of researches in the last years, mainly to verify its effectiveness and toxicity. The family Fabaceae has approximately 300 species, which are popular1y called cow's foot and nail ox, due the format of theirs leafs and are largely used as analgesic, anti-inflammatory and hypoglycemic. The genus Bauhinia, belonging to this family has many species, which are used in diabetes treatment, and it has been researches target showing promising results. Because of that, the objective of this work was to evaluate the hypoglycemic activity of crude extract of Bauhinia holophylla, a species very used in traditional medicine. There are no studies that prove its effectiveness in the diabetes treatment. Swiss mice diabetic (STZSAL and STZEXT) and normoglycemic (CTLSAL and CTLEXT) received treatment for 15 days with the crude ...
3
Henriques, Nathalia Aparecida de Paula Camaforte. "Avaliação da atividade hipoglicemiante do extrato bruto de Bauhinia holophylla (Steud.) em camundongos diabéticos induzidos por estreptozotocina /." Botucatu, 2013. http://hdl.handle.net/11449/108524.
Full textAbstract:
Orientador: José Roberto BosqueiroBanca: Luiz Otávio Regasini
Banca: Débora Cristina Damasceno
Resumo: O termo Diabetes mellitus (DM) descreve uma desordem metabólica caracterizada por hiperglicemia crônica que leva a alterações no metabolismo de carboidratos, lipídeos e proteínas resultante de defeitos na ação, secreção de insulina, ou ambos. Tais alterações levam a sérias consequências no individuo diabético, como perda de peso, aumento dos níveis de lipídeos no sangue podendo levar ao aumento da incidência de doenças cardiovasculares como aterosclerose e infarto. Além disso, pode causar doenças renais e danos à visão, e em casos mais graves, óbito. A incidência de pessoas diabéticas tem aumentado a cada ano, e pesquisas realizadas recentemente apontam que esse é um número que só tende a aumentar nos próximos anos, principalmente devido aos péssimos hábitos alimentares e estilo de vida sedentário. O tratamento para o DM inclui insulinoterapia e o uso de hipoglicemiantes orais. No entanto, sabe-se que esses medicamentos possuem efeitos adversos, como ganho de peso, desconfortos abdominais e diarreias. Partindo dessas informações, a busca de novas alternativas para o tratamento de DM tem crescido muito nos últimos anos. O uso de plantas medicinais no tratamento de diversas doenças, como o diabetes, é feito desde os primórdios da humanidade. Diante disso, a pesquisa envolvendo plantas medicinais com propriedades hipoglicemiantes tem sido alvo dos pesquisadores nos últimos anos, principalmente para comprovação da sua eficácia e verificação da toxicidade das mesmas. A família Fabaceae possui aproximadamente 300 espécies, popularmente conhecidas como pata-de-vaca ou unhade- boi, devido ao formato de suas folhas e são amplamente utilizadas como analgésicos, antiinflamatórios e no tratamento de diabetes. O gênero Bauhinia, pertencente a essa família possui muitas espécies que são utilizadas no tratamento do diabetes. Diante disso, o objetivo desse trabalho foi avaliar a atividade hipoglicemiante do ...
Abstract: The term Diabetes mellitus (DM) defines a metabolic disorder characterized by cnronic hyperglycemia, which leads to alterations in carbohydrate, proteins and lipids metabolism resultant of defects in insulin action andJor secretion. Those alterations lead to serious consequences to diabetic people as weight loss, increase incidence of cardiovascular diseases, renal and optical diseases, and in some cases, death. The incidence of diabetic people is increasing every year and recent1y researches showed that this number will increase on next years, mainly due to bad eating habits and sedentary life style. The treatment of DM inc1udes insulin therapy and the use of oral hypoglycemic agents. However, those medicaments have many collateral effects as weight gain, abdominal discomforts and diarrheas. Based on this information, studies involving new altematives for the treatment of DM are growing in the last years. The use of medicinal plants in the treatment of diverse diseases like diabetes has been done since the beginning of humanity. Due to this, the studies involving medicinal plants with hypoglycemic properties have been the target of researches in the last years, mainly to verify its effectiveness and toxicity. The family Fabaceae has approximately 300 species, which are popular1y called cow's foot and nail ox, due the format of theirs leafs and are largely used as analgesic, anti-inflammatory and hypoglycemic. The genus Bauhinia, belonging to this family has many species, which are used in diabetes treatment, and it has been researches target showing promising results. Because of that, the objective of this work was to evaluate the hypoglycemic activity of crude extract of Bauhinia holophylla, a species very used in traditional medicine. There are no studies that prove its effectiveness in the diabetes treatment. Swiss mice diabetic (STZSAL and STZEXT) and normoglycemic (CTLSAL and CTLEXT) received treatment for 15 days with the crude ...
Mestre
4
Lalej-Bennis, Dalila. "Mise au point et évaluation de la voie nasale d'administration de l'insuline dans le traitement du diabète sucré." Paris 5, 1997. http://www.theses.fr/1997PA05S020.
Full textAbstract:
Apres plus de 10 ans de travaux évaluant les potentialités de l'insuline nasale dans le traitement du diabète sucre, le constat est plutôt négatif : la biodisponibilité est insuffisante et les résultats métaboliques obtenus chez l'homme ne sont pas en rapport avec les espérances des cliniciens. Nous avons repris et complète les travaux de la littérature pour tenter d'améliorer l'efficacité et la tolérance de la formulation nasale et acquérir des données cliniques suffisantes pour conclure sur l'intérêt de l'insuline nasale. Nos résultats montrent que des modifications de la galénique et de la composition de la formulation permettent d'améliorer la biodisponibilité de l'insuline nasale. Les essais cliniques que nous avons réalisés confirment l'intérêt de l'insuline nasale dans la prise en charge du patient diabétique insulino-traite, montrant que l'efficacité métabolique de l'insuline nasale est du même ordre que celle de l'insuline sous-cutanée, avec un gain manifeste dans le confort d'utilisation. Le problème de la tolérance par la muqueuse nasale n'est pas résolu, le lyophilisat étant moins bien toléré que le gel, mais des manifestations d'allure allergique avec une hypereosinophilie à la cytologie nasale sont survenues avec le gel et font suspecter un possible rôle allergisant des dérivés cellulosiques. Dans l'état actuel de nos recherches, le choix de la forme la plus efficace et la mieux tolérée s'oriente plutôt un spray nasal non cellulosique, contenant du glycocholate de sodium comme promoteur de l'absorption. Nos travaux, encore très préliminaires, ont permis de montrer clairement que la voie nasale d'administration de l'insuline a des potentialités en terme de contrôle métabolique et de qualité de vie que l'on ne peut se permettre de négliger dans une pratique dialectologiques clinicienne. Des efforts supplémentaires dans la recherche d'une formulation nasale mieux tolérée doivent être faits, et nécessitent des moyens techniques et financiers qui relèvent, a notre avis, de l'industrie pharmaceutique.
5
Peyrollier, Karine. "Clonage et caractérisation de l'endosulfine-α, un régulateur potentiel des canaux KATP sensibles aux sulfonylurées." Paris 5, 1998. http://www.theses.fr/1998PA05S025.
Full textAbstract:
Les sulfonylurees hypoglycémiants sont les médicaments les plus utilisés dans le traitement du diabète de type II. Un récepteur spécifique de ces molécules a récemment été cloné. Il est étroitement associe à une sous-unité de la famille KIR 6. X pour former un canal K A T P fonctionnel. Ce canal est localise dans de nombreux tissus comme le système nerveux central, les muscles squelettiques, le cœur, le pancréas l'existence d'un ligand endogène se trouvant à proximité de ce canal a été prouvée, dans le système nerveux central de rat, de porc et de mouton. Ce ligand endogène, appelé endosulfine existe sous deux formes moléculaires, et la forme a été purifiée. Les séquences partielles obtenues après digestion trypsique de la protéine, ont montrées de fortes homologies avec une protéine précédemment purifiée l'ARPP-19. L'ARPP-19 ayant été cloné chez le bœuf et l'endosulfine- chez le porc, nous nous demandions si les différences observées reflétaient les différences d'espèces ou s’il s'agissait de deux protéines distinctes. Pour répondre à cette question, l'endosulfine- et l'ARPP-19 ont été cloné chez le porc, le bœuf, le rat et la souris. Il est alors apparu que ces deux protéines étaient différentes mais avaient de fortes homologies de séquences. L'ARPP-19 et l'endosulfine- sont très conservées entre les espèces ce qui indique leur importance. La répartition tissulaire de ces deux protéines a été envisagée. L'endosulfine- a été localisée dans tous les tissus à un état basal, mais en plus grande quantité dans les tissus du système nerveux central, particulièrement dans le cervelet, ainsi que dans le muscle squelettique et les ilots de Langerhans. Quant à l'ARPP-19, sa répartition tissulaire est très différente de celle de l'endosulfine. En effet, cette protéine a été détectée à un niveau basal dans tous les tissus, mais elle est particulièrement abondante dans le bulbe olfactif, le rein et le pancréas.
6
Chang, Chih-Shiang, and 張智翔. "Study on the hypoglycemic effect of the ethyl acetate extract of Curcubita moschata fruit in animal models." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/43652146121745893153.
Full textAbstract:
碩士國立屏東科技大學
生物科技系所
104
The fruit of Cucurbita moschata has been confirmed to contain hypoglycemic components, and which can be further concentrated by partitioning between ethyl acetate (EA) and water to distribute them to the EA layer. The purpose of this study is to investigate the hypoglycaemic effect of the EA extract in diabetic animal models. To establish type 2 diabetic models, mice were fed with high-fat diet to induce insulin resistance, followed by injection of streptozotocin (stz) to destroy the pancreatic cell. The mice were then fed with the EA extract of pumpkin for 23 days. Consequently, the EA extract obviously reduced the level of blood in glucose oral glucose tolerance tests, and the fasting blood glucose of EA extract-fed mice was significantly decreased. Meanwhile, normal mice fed with the EA extract did not exhibit any obviously side effect hypoglycaemic. These result support that the EA extract of pumpkin has activity in vivo. However, it was also revealed that the method of using high-fat diet plus STZ injection to diet established by 2 diabetes model not develop type diabetes is not stable, and needs to be further optimized.
7
Rahimi, Yasmeen. "The role of pyruvate dehydrogenase kinase in glucose and ketone body metabolism." Thesis, 2014. http://hdl.handle.net/1805/3798.
Full textAbstract:
Indiana University-Purdue University Indianapolis (IUPUI)The expression of pyruvate dehydrogenase kinase (PDK) 2 and 4 are increased in the fasted state to inactivate the pyruvate dehydrogenase complex (PDC) by phosphorylation to conserve substrates for glucose production. To assess the importance of PDK2 and PDK4 in regulation of the PDC to maintain glucose homeostasis, PDK2 knockout (KO), PDK4 KO, and PDK2/PDK4 double knockout (DKO) mice were generated. PDK2 deficiency caused higher PDC activity and lower blood glucose levels in the fed state while PDK4 deficiency caused similar effects in the fasting state. DKO intensified these effects in both states. PDK2 deficiency had no effect on glucose tolerance, PDK4 deficiency produced a modest effect, but DKO caused a marked improvement, lowered insulin levels, and increased insulin sensitivity. However, the DKO mice were more sensitive than wild-type mice to long term fasting, succumbing to hypoglycemia, ketoacidosis, and hypothermia. Stable isotope flux analysis indicated that hypoglycemia was due to a reduced rate of gluconeogenesis. We hypothesized that hyperglycemia would be prevented in DKO mice fed a high saturated fat diet for 30 weeks. As expected, DKO mice fed a high fat diet had improved glucose tolerance, decreased adiposity, and were euglycemic due to reduction in the rate of gluconeogenesis. Like chow fed DKO mice, high fat fed DKO mice were unusually sensitive to fasting because of ketoacidosis and hypothermia. PDK deficiency resulted in greater PDC activity which limited the availability of pyruvate for oxaloacetate synthesis. Low oxaloacetate resulted in overproduction of ketone bodies by the liver and inhibition of ketone body and fatty acid oxidation by peripheral tissues, culminating in ketoacidosis and hypothermia. Furthermore, when fed a ketogenic diet consisting of low carbohydrate and high fat, DKO mice also exhibited hypothermia, ketoacidosis, and hypoglycemia. The findings establish that PDK2 is more important in the fed state, PDK4 is more important in the fasted state, survival during long term fasting depends upon regulation of the PDC by both PDK2 and PDK4, and that the PDKs are important for the regulation of glucose and ketone body metabolism.
8
Gauthier, Nicolas. "Physiopathologie des maladies métaboliques héréditaires des acyls-Coenzyme A révélée par l’étude d’un modèle animal déficient en 3-hydroxy-3-méthylglutaryl-Coenzyme A lyase." Thèse, 2013. http://hdl.handle.net/1866/10098.
Full textAbstract:
La plupart des conditions détectées par le dépistage néonatal sont reliées à l'une des enzymes qui dégradent les acyls-CoA mitochondriaux. Le rôle physiopathologique des acyls-CoA dans ces maladies est peu connue, en partie parce que les esters liés au CoA sont intracellulaires et les échantillons tissulaires de patients humains ne sont généralement pas disponibles. Nous avons créé une modèle animal murin de l'une de ces maladies, la déficience en 3-hydroxy-3-methylglutaryl-CoA lyase (HL), dans le foie (souris HLLKO). HL est la dernière enzyme de la cétogenèse et de la dégradation de la leucine. Une déficience chronique en HL et les crises métaboliques aigües, produisent chacune un portrait anormal et distinct d'acyls-CoA hépatiques. Ces profils ne sont pas prévisibles à partir des niveaux d'acides organiques urinaires et d'acylcarnitines plasmatiques. La cétogenèse est indétectable dans les hépatocytes HLLKO. Dans les mitochondries HLLKO isolées, le dégagement de 14CO2 à partir du [2-14C]pyruvate a diminué en présence de 2-ketoisocaproate (KIC), un métabolite de la leucine. Au test de tolérance au pyruvate, une mesure de la gluconéogenèse, les souris HLLKO ne présentent pas la réponse hyperglycémique normale. L'hyperammoniémie et l'hypoglycémie, des signes classiques de plusieurs erreurs innées du métabolisme (EIM) des acyls-CoA, surviennent de façon spontanée chez des souris HLLKO et sont inductibles par l'administration de KIC. Une charge en KIC augmente le niveau d'acyls-CoA reliés à la leucine et diminue le niveau d'acétyl-CoA. Les mitochondries des hépatocytes des souris HLLKO traitées avec KIC présentent un gonflement marqué. L'hyperammoniémie des souris HLLKO répond au traitement par l'acide N-carbamyl-L-glutamique. Ce composé permet de contourner une enzyme acétyl-CoA-dépendante essentielle pour l’uréogenèse, le N-acétylglutamate synthase. Ceci démontre un mécanisme d’hyperammoniémie lié aux acyls-CoA. Dans une deuxième EIM des acyls-CoA, la souris SCADD, déficiente en déshydrogénase des acyls-CoA à chaînes courtes. Le profil des acyls-CoA hépatiques montre un niveau élevé du butyryl-CoA particulièrement après un jeûne et après une charge en triglycérides à chaîne moyenne précurseurs du butyryl-CoA.Most conditions detected by expanded newborn screening result from deficiency of one of the enzymes that degrade acyl-CoA esters in mitochondria. The role of acyl-CoAs in the pathophysiology of these disorders is poorly understood, in part because CoA esters are intracellular and samples are not generally available from human patients. We created a mouse model of one such condition, deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase (HL), in liver (HLLKO mice). HL catalyses a reaction of ketone body synthesis and of leucine degradation. Chronic HL deficiency and acute crises each produced distinct abnormal liver acyl-CoA patterns, which would not be predictable from levels of urine organic acids and plasma acylcarnitines. In HLLKO hepatocytes, ketogenesis was undetectable. Measures of Krebs cycle flux diminished following incubation of HLLKO mitochondria with the leucine metabolite 2-ketoisocaproate (KIC). HLLKO mice also had suppression of the normal hyperglycemic response to a systemic pyruvate load, a measure of gluconeogenesis. Hyperammonemia and hypoglycemia, cardinal features of many inborn errors of acyl-CoA metabolism, occurred spontaneously in some HLLKO mice and were inducible by administering KIC. KIC loading also increased levels of several leucine-related acyl-CoAs and reduced acetyl-CoA levels. Ultrastructurally, hepatocyte mitochondria of KIC-treated HLLKO mice show marked swelling. KIC-induced hyperammonemia improved following administration of carglumate (N-carbamyl-L-glutamic acid), which bypasses an acetyl-CoA-dependent reaction essential for urea cycle function, thus demonstrating an acyl-CoA-related mechanism for this complication. In a second animal model of an inborn error of acyl-CoA metabolism, short chain acyl-CoA dehydrogenase (SCAD)-deficient mice, the main finding in liver acyl-CoAs is increased butyryl-CoA, particularly during fasting or after enteral loading with medium chain triglyceride precursor of butyryl-CoA.
9
McNeilly, A. D., Ritchie Williamson, D. J. Balfour, C. A. Stewart, and C. Sutherland. "A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin." 2012. http://hdl.handle.net/10454/6095.
Full textAbstract:
AIMS/HYPOTHESIS: We previously demonstrated that animals fed a high-fat (HF) diet for 10 weeks developed insulin resistance and behavioural inflexibility. We hypothesised that intervention with metformin would diminish the HF-feeding-evoked cognitive deficit by improving insulin sensitivity. METHODS: Rats were trained in an operant-based matching and non-matching to position task (MTP/NMTP). Animals received an HF (45% of kJ as lard; n = 24), standard chow (SC; n = 16), HF + metformin (144 mg/kg in diet; n = 20) or SC + metformin (144 mg/kg in diet; n = 16) diet for 10 weeks before retesting. Body weight and plasma glucose, insulin and leptin were measured. Protein lysates from various brain areas were analysed for alterations in intracellular signalling or production of synaptic proteins. RESULTS: HF-fed animals developed insulin resistance and an impairment in switching task contingency from matching to non-matching paradigm. Metformin attenuated the insulin resistance and weight gain associated with HF feeding, but had no effect on performance in either MTP or NMTP tasks. No major alteration in proteins associated with insulin signalling or synaptic function was detected in response to HF diet in the hypothalamus, hippocampus, striatum or cortex. CONCLUSIONS/INTERPRETATION: Metformin prevented the metabolic but not cognitive alterations associated with HF feeding. The HF diet protocol did not change basal insulin signalling in the brain, suggesting that the brain did not develop insulin resistance. These findings indicate that HF diet has deleterious effects on neuronal function over and above those related to insulin resistance and suggest that weight loss may not be sufficient to reverse some damaging effects of poor diet.
10
Kickstein, E., S. Krauss, P. Thornhill, D. Rutschow, R. Zeller, J. Sharkey, Ritchie Williamson, et al. "Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling." 2010. http://hdl.handle.net/10454/6051.
Full textAbstract:
Hyperphosphorylated tau plays an important role in the formation of neurofibrillary tangles in brains of patients with Alzheimer's disease (AD) and related tauopathies and is a crucial factor in the pathogenesis of these disorders. Though diverse kinases have been implicated in tau phosphorylation, protein phosphatase 2A (PP2A) seems to be the major tau phosphatase. Using murine primary neurons from wild-type and human tau transgenic mice, we show that the antidiabetic drug metformin induces PP2A activity and reduces tau phosphorylation at PP2A-dependent epitopes in vitro and in vivo. This tau dephosphorylating potency can be blocked entirely by the PP2A inhibitors okadaic acid and fostriecin, confirming that PP2A is an important mediator of the observed effects. Surprisingly, metformin effects on PP2A activity and tau phosphorylation seem to be independent of AMPK activation, because in our experiments (i) metformin induces PP2A activity before and at lower levels than AMPK activity and (ii) the AMPK activator AICAR does not influence the phosphorylation of tau at the sites analyzed. Affinity chromatography and immunoprecipitation experiments together with PP2A activity assays indicate that metformin interferes with the association of the catalytic subunit of PP2A (PP2Ac) to the so-called MID1-alpha4 protein complex, which regulates the degradation of PP2Ac and thereby influences PP2A activity. In summary, our data suggest a potential beneficial role of biguanides such as metformin in the prophylaxis and/or therapy of AD.
Book chapters on the topic "Animals Hypoglycemia"
1
Gonzalez, Anthony L., and Deborah C. Silverstein. "Hypoglycemia." In Textbook of Small Animal Emergency Medicine, 719–25. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2018. http://dx.doi.org/10.1002/9781119028994.ch111.
Full text
2
Koenig, Amie. "Hypoglycemia." In Small Animal Critical Care Medicine, 295–99. Elsevier, 2009. http://dx.doi.org/10.1016/b978-1-4160-2591-7.10069-4.
Full text
3
Koenig, Amie. "Hypoglycemia." In Small Animal Critical Care Medicine, 352–57. Elsevier, 2015. http://dx.doi.org/10.1016/b978-1-4557-0306-7.00066-0.
Full text
4
Akinyinka Akinwumi, Kazeeem, Oluwole Olusoji Eleyowo, and Omolara Omowunmi Oladipo. "A Review on the Ethnobotanical Uses, Phytochemistry and Pharmacology Effect of Luffa cylindrica." In Pharmacognosy - Medicinal Plants [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.98405.
Full textAbstract:
Luffa cylindrica, popularly known as sponge gourd is a tropic and sub-tropical fibrous plant with fruits containing black seeds. The fruit is consumed by humans as a vegetable in many parts of Asia, while different parts of the plant are used for cosmetics and as medicine in many parts of the globe. The plant has been used in the treatment of many ailments including nose cancer, snake venom, wound healing, edema, enterobiasis, filaria, whooping cough, stomach upset, stomach pain and malaria. Many health-promoting compounds such as flavonoids (apigenin-7- glucuronide luteolin-7-O-β-D-glucuronide methyl ester, -O-feruloyl-β-D-glucose, luteolin-7-O-β-D-glucuronide methyl ester), phenolics acids (p-Coumaric, gallic, caffeic, chlorogenic), triterpenoids (oleanolic acid and echinocystic acid), saponins (Lucyoside A-M), tannins (catechin), ribosome-inactivating proteins (α- luffin), carotenoids (9 -cis neoxanthin, all-trans-lutein, all-trans-β-carotene), chlorophylls (chlorophyll a and b, pheophytin), cucurbitacin B and gypsogenin have been detected or isolated from different parts of the plants. Extracts of the plant and isolated compounds have wide spectrum pharmacological activities and have been shown to possess antiemetic, antidiabetic, antiviral, wound healing, anticancer, antipyretic, anti-inflammatory, antifungal, anti-bacteria, anthelmintic, hypoglycemic and antihyperglycemic, anti-inflammatory, antioxidant activity, and hepato-protective effects in animal models. However, further information is needed on its safety and mechanisms of action. The present article is an updated review of the ethnobotanical uses, pharmacological actions, phytochemistry, safety, and future application of Luffa cylindrica in translational medicine.
Conference papers on the topic "Animals Hypoglycemia"
1
Pradana, Dhigna Luthfiyani Citra, Eldiza Puji Rahmi, and Annisa Farida Muti. "Hypoglycemic Effect of Moringa oleifera Aqueous Extract in Diabetic Animal Studies: A Mechanisms Review." In 4th International Conference on Sustainable Innovation 2020–Health Science and Nursing (ICoSIHSN 2020). Paris, France: Atlantis Press, 2021. http://dx.doi.org/10.2991/ahsr.k.210115.117.
Full text
2
Folts, J. D. "A MODEL OF ACUTE PLATELET THROMBUS FORMATION IN STENOSED CORONARY AND CAROTID ARTERIES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643712.
Full textAbstract:
There is currently a great deal of interest in the diagnosis and treatment of unstable angina and silent ischemia.Many feel that these syndromes are due, in part, to periodic accumulation of platelet thrombi which subsequently embolize.In addition, anti-piatelet therapy is also considered necessary for patients after coronary artery bypass grafts (CABG'S), balloon angioplasty, and thrombolysis. Currently the two antiplatelet agents most commonly prescribed for the patient conditions mentioned above are aspirin (ASA), alone or in combination with dipyridamole (Dip). ASA reduces cardiac events in patients with unstable angina, and prolongs CABG graft patency. The addition of Dip to ASA therapy is very confusing since most studies done compared ASA + Dip to placebo. In several studies however,when an ASA group was compared to an ASA + Dip group there was no significant difference.We have developed and will describe ananimal model of coronary artery stenosis in the dog and the pig, or carotid arterystenosis in the monkey and the rabbit, with intimal damage, that simulates some ofthe conditions that exist in patients with coronary or carotid artery disease. The artery to be studied is dissected outand blood flow is continuously measured with an electromagnetic flowmeter probe. As acute platelet thrombus formation (APTF) developes in the stenosed lumen, the blood flow declines to low levels, producing ischemia until the thrombus emobolizesdistally resulting in abrupt restoration of blood flow. These cyclical flow reductions (CFR's), when they occur in the coronaries, produce ECG changes identical to those observed in patients with silent ischemia and unstable angina. They also produce significant transient regional dyskinesis of the ventricular wall, which resolves when blood flow is restored. Histologic examination of myocardial tissue in the bed distal to the stenosis shows focal areas of ischemic change presumably caused by the embolized platelet emboli.We have examined factors which exacerbate the size and frequency of these CFR"ssuch as; IV infusion of epinephrine (E) 0.4 μg/kg/min for 15 min, ventilating the animals with cigarette smoke, infusing nicotine IV, or placing chewing tobacco under the tongue.We have examined four groups of agentswhich prevent APTF in our model.1. Antiplatelet agents including ASA, indomethacin, ibuprofen and several other NSAI agentsas well as several experimental thromboxane synthetase inhibitors. These agents all block the production of TXA2and inhibit APTF in our model. Unfortunately the IV infusion of E reinstates APTtemporarily (by another biochemical pathway) until the E is metabolized. High (2-4 mg/kg) doses of Dip, alone or with sub threshold dose of ASA does nothing to I APTF.However,0.6mg/kg of chi orpromaz i ne abolishes APTF in all four species and protects agents renewal of APTF by E.2. Dietary Substances In our model, caffeine 10 mg/kg, or the extract from two garlic cloves, or enough ethanol to achieve a blood alcohol level of 0.07 mg% all significantly inhibit or abolish APTF in our model.3. Metabolic Inhibitors POCA, an oral hypoglycemic agent, which inhibits mitochondrial beta oxidation of fatty acids also inhibits APTF in our model possibly by reducing ATP production in the platelet.4. We have studied a monoclonal antibody(developed by Dr. Barry Coller) to the platelet I Ib�I I la glycoprotein receptor where fibrinogen binds platelets into aggregates and ultimately leads to APTF. This antibody 0.3 mg/kg/completely inhibits APTF, and also strongly inhibits in vitro platelet aggregation in response to either ADP or collagen given alone or each combined with E. This antibody is the most potent inhibitor of APTF that we have studied.