Academic literature on the topic 'Streptozotocin model'

<p> Diabetes is a group of metabolic diseases where the body&rsquo;s pancreas does not produce enough insulin or does not properly respond to insulin produced, resulting in high blood sugar levels over a prolonged period. There are several different types of diabetes, but the most common forms are type 1 and type 2 diabetes. Type 1 diabetes Mellitus (T1DM) can occur at any age, but is most commonly diagnosed from infancy to late 30s. If a person is diagnosed with type 1 diabetes, their pancreas produces little to no insulin, and the body&rsquo;s immune system destroys the insulin-producing cells in the pancreas. Those diagnosed with type 1 diabetes must inject insulin several times every day or continually infuse insulin through a pump, as well as manage their diet and exercise habits. If not treated appropriately, it can cause serious complications such as cardiovascular disease, stroke, kidney failure, foot ulcers, and damage to eyes.</p><p> During the past decade, researchers have developed artificial pancreas (AP) to ease management of diabetes. AP has three components: continuous glucose monitor (CGM), insulin pump, and closed-loop control algorithm. Researchers have developed algorithms based on control techniques such as Proportional Integral Derivative (PID) and Model Predictive Control (MPC) for blood glucose level (BGL) control; however, variability in metabolism between or within individuals hinders reliable control. </p><p> This study aims to develop an adaptive algorithm using Artificial Neural Networks (ANN) based Model Predictive Control (NN-MPC) to perform proper insulin injections according to BGL predictions in diabetic rats. This study is a ground work to implement NN-MPC algorithm on real subjects. BGL data collected from diabetic rats using CGM are used with other inputs such as insulin injection and meal information to develop a virtual plant model based on a mathematical model of glucose&ndash;insulin homeostasis proposed by Lombarte et al. Since this model is proposed for healthy rats; a revised version on this model with three additional equations representing diabetic rats is used to generate data for training ANN which is applicable for the identi?cation of dynamics and the glycemic regulation of rats. The trained ANN is coupled with MPC algorithm to control BGL of the plant model within the normal range of 100 to 130 mg/dl by injecting appropriate amount of insulin. The ANN performed well with less than 5 mg/dl error (2%) for 5-minute prediction and about 15 mg/dl error (7%) for 30-minute prediction. In &not;&not;addition, the NN-MPC algorithm kept BGL of diabetic rats more than 90 percent of the time within the normal range without hyper/hypo-glycaemia.</p>

Objectives: To date little is known of the interaction between diabetes and sex hormones in the vasculature. A number of studies suggest that premenopausal diabetic women loose their gender based cardiovascular protection. However, there is insufficient evidence to explain the mechanism underlying the loss of this gender based cardioprotection in premenopausal diabetic women. The objectives of this study were to investigate whether there is a gender difference in the aortic endothelial function in · streptozotocin (STZ, 58 mg/kg, iv)-induced diabetic rats, and the potential role of superoxide and cyclooxygenase (COX) metabolites in diabetes-induced vascular dysfunction.

Elevated sympathetic nervous system (SNS) tone contributes to excess cardiac mortality associated with type 2 diabetes mellitus (T2DM). Chronic SNS stimulation has detrimental effects to the heart, in particular, with its cell signaling abilities. (R)-[11C]Rolipram small animal positron emission tomography (PET), an noninvasive nuclear imaging modality, was used to assess phosphodiesterase-4 (PDE4) alterations in a high fat diet (HFD), streptozotocin (STZ) induced model of hyperglycemia in rats. Prior to investigation in the animal model, characterization of (R)-[11C]rolipram small animal PET was completed. (R)-[11C]Rolipram binds specifically to PDE4 in the rat heart demonstrated by competitive blockade with (R)-rolipram with the PDE4 enzyme susceptible to saturation with increasing injected masses of unlabeled rolipram. (R)-[11C]Rolipram cardiac retention was elevated by acute norepinephrine stimulation via desipramine pharmacologic challenge. Quantitative (R)-[11C]rolipram PET was highly reproducible in the heart and presents an ideal avenue to investigate PDE4 alterations. (R)-[11C]rolipram small animal PET did not reveal changes in PDE4 expression and activity in STZ-treated hyperglycemic animals compared to STZ-treated euglycemic and control groups. In vitro measures of PDE4 enzyme expression and activity, with or without desipramine, were also not altered between treatment groups. Although (R)-[11C]rolipram small animal PET does not reveal PDE4 alterations in this animal model of diabetes, its utility to assess PDE4 alterations in other over active SNS pathologies, such as heart failure and obesity, remains.

Thesis submitted in fulfilment of the requirements for the Doctor of Technology: Biomedical Technology In the Faculty of Health and Wellness At the CAPE PENINSULA UNIVERSITY OF TECHNOLOGY, 2012<br>Diabetes mellitus is a major health problem not only in urban, but also in the rural areas and is diagnosed by the presence of high glucose levels in the blood. Oxidative stress is known to be actively involved in the onset and progression of diabetes and its complications. Antioxidants have important roles in biological systems by scavenging free radicals which may result in oxidative damage of biological molecules such as lipids, proteins and DNA. Red palm oil, originally from the tropical area of Africa, generally consumed as cooking oil, is known to have some beneficial health effects due to the presence of lipid soluble antioxidants such as carotenoids, tocopherols and tocotrienols. It also contains almost an equal proportion of both saturated and unsaturated fatty acids which makes it distinctive from other vegetable oils. Rooibos, on the other hand, is grown in the Cederberg area of the Western Cape in South Africa and it is commonly consumed as a beverage. It contains a complex profile of water soluble antioxidants (flavonoids) and its health promoting potentials have been reported extensively. Some of the flavonoids present in rooibos include aspalathin, nothofagin, quercetin, rutin and orientin. The objective of this research project was to examine the potential beneficial effects of the dietary intake of red palm oil and rooibos on streptozotocin-induced hyperglycaemia and its influence on the antioxidant status and some biochemical parameters in male Wistar rats. The preliminary phase of this study was designed to investigate the biochemical effects of these two plant products at different dosages following consumption for a period of 7 weeks. The preliminary study did not reveal any adverse effects of the different dosages of red palm oil (1 ml, 2 ml and 4 ml) and rooibos (2%, 4% and 6%) on the experimental rats following dietary intake for 7 weeks. However, these natural products showed an improvement in the antioxidant status of the rats at the different doses. Using a single dose each of both plant products from the preliminary study, the main study was performed to investigate the influence of these two plant products singly and in combination on the blood and liver of streptozotocin-induced hyperglycaemic male Wistar rats. In the main study, streptozotocin (50 mg/kg) dissolved in 0.1 M citrate buffer (pH 4.5) through intramuscular injection was used for the induction of diabetes which was confirmed by the presence of high blood glucose after 72 hours. Red palm oil or rooibos extract alone did not have any effect on the control of blood glucose in the diabetic rats. The dietary intake of the combined treatment with red palm and rooibos had more health promoting effects on the diabetic rats which included a decrease in blood glucose, glycosylated haemoglobin, fructosamine and increased insulin levels. There was a marked increase in liver glycogen levels in all the diabetic groups. Treatment with rooibos alone showed a decrease in glycogen levels in the diabetic rats. The presence of liver enzymes in the serum, commonly used as indicators of liver damage was increased in all the diabetic rats. However, the combined treatment of diabetic rats with red palm oil and rooibos protected the liver from injury. Red palm oil improved high density lipoprotein cholesterol levels (HDL-cholesterol) in the diabetic rats. There was no effect on the activity of glucokinase, the first enzyme in the the glycolytic pathway in both the untreated and treated diabetic rats. However, the activity of pyruvate kinase, the last enzyme in the glycolytic pathway was reduced in all the diabetic groups. The combined treatment with both red palm and rooibos increased the activity of pyruvate kinase. Oxidative stress was confirmed in the diabetic rats with an increase in the plasma thiobarbituric acid reactive substances (TBARS), an indicator of lipid peroxidation. Treatment of diabetic rats with rooibos and the combination of red palm oil and rooibos brought plasma TBARS to a level that was not significantly different from the normal control group. There was a non-significant reduction of total glutathione in the non-treated and treated diabetic groups. A non-significant increase in the activity of liver catalase was observed in all the treated diabetic groups. The activity of superoxide dismutase was significantly decreased in the liver of diabetic rats. Diabetic rats treated with red palm oil, rooibos and the combined treatment showed an increased activity of superoxide dismutase in the liver. Red palm oil and the combined treatment increased the activity of glutathione peroxidase in both the red blood cells and liver of diabetic rats. Red palm oil, rooibos and their combined treatments also improved the plasma antioxidant capacity such as ferric reducing antioxidant power (FRAP) and oxygen reducing absorbance capacity (ORAC) in the diabetic rats. In conclusion, oxidative stress is actively involved in the progression of diabetes mellitus. Red palm oil and rooibos, most especially their combined treatment showed significant beneficial health promoting effects in the diabetic rats. The remarkable effects of the combined treatment of red palm oil and rooibos in the diabetic rats could be due to their antioxidant profiles. Based on the findings from this study, it can be adduced that these plant products could help in the management of diabetes and its complications and therefore, suggested the need for further research studies on antioxidant therapy in the management of diabetes mellitus.

Diabetes mellitus (DM) and hyperglycemia contribute to sympathetic nervous system (SNS) activation and cardiovascular dysfunction. SNS activation and increased norepinephrine levels downregulate cardiac β-adrenergic receptors (β-AR). The ADMIRE-HF trial identified reduced cardiac SNS innervation as an independent prognostic marker in heart failure. The β-AR antagonist [3H]-CGP12177 was used to quantify cardiac β-AR in ex vivo biodistribution studies in streptozotocin (STZ)-treated rats after 8 weeks of sustained hyperglycemia, and in the Zucker Diabetic Fatty (ZDF) rat model of type-2 diabetes at the onset of hyperglycemia (10 weeks of age) and after a sustained period of hyperglycemia (16 weeks of age). In some STZ rats, insulin was provided at the onset of hyperglycemia, or after a sustained period of hyperglycemia. Insulin treatment at both time points prevented reduced [3H]-CGP12177 binding (33-38% compared to controls) observed in STZ hyperglycemics. ZDF β-ARs were intact at 10 weeks but became reduced (16-25% relative to the Zucker leans) following 6 weeks of hyperglycemia. This work supports that cardiac β-AR are reduced in models of DM and that restoring insulin signalling to maintain glycemic control can normalize β-AR density whether provided early or after a period of sustained hyperglycemia.

Severas altera¸c~oes no metabolismo energ´etico, no consumo de glicose e na sinaliza¸c~ao de insulina cerebral est~ao presentes na doen¸ca de Alzheimer (DA). O modelo animal da DA obtido pela administra¸c~ao intracerebroventricular de estreptozotocina (STZ-icv) em ratos induz um estado de resist^encia `a insulina no c´erebro associado `a disfun¸c~oes colin´ergicas e a d´eficits cognitivos, tornando-o um dos poucos modelos experimentais da forma espor´adica da DA. Este trabalho tem como objetivo caracterizar, neste modelo, as disfun¸c~oes sin´apticas na via hipocampo - c´ortex pr´e-frontal medial (CA1-CPFm) e testar se o tratamento com nicotina ´e capaz de prevenir as disfun¸c~oes sin´apticas e reverter os preju´?zos cognitivos induzido pelo STZ-icv. Para isso, ratos Wistar receberam STZ e foram submetidos a 20 dias de tratamento com nicotina. Dois dias depois, foram realizados nos animais teste de campo aberto e de reconhecimento de objeto. Em seguida os animais foram anestesiados com uretana para que os registros eletrofisiol´ogicos fossem realizados. Um eletrodo foi utilizado para estimular CA1 com pulso pareado e potenciais de campo p´os-sin´apticos (fPSP1) e sua facilita¸c~ao (fPSP2) foram registradas por um eletrodo no CPFm. Ap´os 30 minutos de linha de base, uma estimula¸c~ao em alta frequ^encia foi aplicada para induzir a potencia¸c~ao de longa dura¸c~ao (LTP), seguido de mais quatro horas de registro. Outro grupo experimental foi realizado para avaliar o efeito de longo prazo da STZ-icv e do tratamento com nicotina. Neste grupo, testes comportamentais e eletrofisiol´ogicos foram realizados 60 dias ap´os o fim do tratamento. Independentemente do tempo, os resultados indicam que a STZ produziu uma redu¸c~ao na indu¸c~ao e na manuten¸c~ao da LTP, mas a facilita¸c~ao por pulso pareado (PPF = fPSP2 / fPSP1) mostra que a STZ prejudica a plasticidade pr´e-sin´aptica apenas a curto prazo. O tratamento com nicotina atenua a disfun¸c~ao na LTP induzida pela STZ. Al´em disso, apenas o tratamento de nicotina tamb´em ´e capaz de reduzir a plasticidade pr´e-sin´aptica no grupo controle dois dias ap´os o fim do tratamento. Estes resultados tamb´em est~ao associados com os dados comportamentais, uma vez que a nicotina reverteu os d´eficits de mem´oria de reconhecimento nos animais STZ mas manteve o comportamento explorat´orio reduzido. Sugerimos com isso que o sistema colin´ergico, que desempenha um papel importante em fun¸c~oes cognitivas e na LTP, est´a afetado nos animais injetados com STZ e o tratamento cr^onico com nicotina consegue reduzir os danos na plasticidade sin´aptica e comportamentais, induzidos pela STZ.<br>Severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to play an important role in early stage of alzheimer disease (AD) pathology. Intracerebroventricular administration (icv) of streptozotocin (STZ) in rats can induce an insulin-resistant brain state associated with cholinergic dysfunctions and memory impairments, which make it a suitable experimental model of the sporadic form of AD. The present work aimed to extend the characterization of this model by probing synaptic plasticity dysfunctions in the medial prefrontal cortex (mPFC)- hippocampal (CA1) pathway and test if nicotine can prevent synaptic dysfunction and revert cognitive impairment induced by icv STZ. Here, Wistar rats received bilateral microinjection of STZ and were submitted to 20 days of nicotine treatment. After 2 days of withdrawing the subjects were submitted to open field and object recognition tests. After that, animals were anesthetized with urethane for electrophysiological tests. A twisted bipolar electrode was used to stimulate posterior-dorsal hippocampus (CA1/subiculum) with paired-pulse. Basal field post-synaptic potentials (fPSP1) and facilitated responses (fPSP2) were recorded by a monopolar electrode in the medial mPFC. After 30min of baseline, high frequency stimulation was applied to induce long-term potentiation (LTP) and additional four hours of electrophysiological recordings was performed. Another experimental group was performed to evaluate the long term effect of both icv STZ and nicotine treatment. In this group behavioral and electrophysiological tests were performed with 60 days after chronic treatment. Independently of time, our results indicate that STZ produced a significant decrease in the induction and maintenance of LTP, but paired pulse facilitation (PPF = fPSP2/fPSP1) shows that only the short-term pre-synaptic plasticity was impaired after STZ injection. The nicotine treatment attenuates the STZ-induced LTP dysfunction in the CA1-mPFC pathway. However, just the nicotine treatment (in control group) can reduce pre-synaptic plasticity two days after chronic treatment. These results are also associated with behavioral data, since nicotine treatment reversed the deficits in recognition memory of STZ animals but maintained the reduced exploratory behavior. We suggest that the brain cholinergic system, which plays a role in cognition function and LTP, is affected in STZ injected animals and chronic treatment with nicotine can attenuate the STZ-induced synaptic plasticity and behavioral dysfunctions.