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Type 2 Diabetic Rats (type 2 + diabetic_rat)
Selected AbstractsSEQUENTIAL ACTIVATION OF THE REACTIVE OXYGEN SPECIES/ANGIOTENSINOGEN/RENIN,ANGIOTENSIN SYSTEM AXIS IN RENAL INJURY OF TYPE 2 DIABETIC RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2008Kayoko Miyata SUMMARY 1The present study was performed to test the hypothesis that the reactive oxygen species (ROS),angiotensinogen (AGT),renin angiotensin system (RAS) axis is sequentially activated in the development of diabetic nephropathy in Zucker diabetic fatty (ZDF) obese rats. 2Genetic pairs of male ZDF obese and control ZDF lean rats (n = 12 of each species) were killed every 3 weeks from 12 to 21 weeks of age (n = 6 at each time point). 3The ZDF obese rats developed diabetes mellitus at 12 weeks. At that time, urinary excretion rates of 8-isoprostane were similar between the groups; however, urinary 8-isoprostane levels were significantly increased at 15 weeks in ZDF obese rats compared with controls (36 ± 6 vs 15 ± 2 ng/day, respectively). At 15 weeks, protein levels of cortical angiotensinogen were similar between groups; however, cortical angiotensinogen levels were significantly increased at 18 weeks in ZDF obese rats compared with controls (relative ratio of 2.32 ± 0.21 vs 1.00 ± 0.20, respectively). At 12 weeks, angiotensin (Ang) II-like immunoreactivity was similar between groups in both the glomeruli and tubules; however, AngII-like immunoreactivity was increased significantly at 21 weeks in ZDF obese rats compared with controls (relative ratios of 1.98 ± 0.55 vs 1.00 ± 0.03, respectively, for glomeruli and 1.58 ± 0.16 vs 1.00 ± 0.13, respectively, for tubules). Moreover, at 21 weeks, the desmin-positive area in the glomeruli (0.63 ± 0.08 vs 0.22 ± 0.05%) and Masson's trichrome stain-positive area in the interstitium (4.97 ± 0.05 vs 3.18 ± 0.41%) were significantly increased in ZDF obese rats compared with controls, even though these differences had not been observed earlier. 4These data suggest that the sequential activation of the ROS,AGT,RAS axis plays an important role in the development of diabetic nephropathy in ZDF obese rats. [source] Antihyperlipidemic activity of 3-hydroxymethyl xylitol, a novel antidiabetic compound isolated from Casearia esculenta (Roxb.) root, in streptozotocin-diabetic ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2010Govindasamy Chandramohan Abstract Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound, 3-hydroxymethyl xylitol (3-HMX), has been isolated, and its optimum dose has been determined in a short duration study and patented. In addition, the long-term effect of 3-HMX in type 2 diabetic rats on carbohydrate metabolism was investigated, and its antihyperglycemic effect was shown previously (Chandramohan et al., Eur J Pharmacol 2008;590:437,443). In this study we investigated the effect of 3-HMX on plasma and tissue lipid profiles in streptozotocin-induced diabetic rats. Diabetes was induced in adult male albino rats of the Wistar strain, weighing 180,200 g, by administration of streptozotocin (40 mg/kg of body weight) intraperitoneally. The normal and diabetic rats were treated with 3-HMX (40 mg/kg BW/day) for 45 days. The levels of total cholesterol, triglycerides, free fatty acids, and phospholipids were assayed in the plasma besides lipoprotein-cholesterol (high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and very low density lipoprotein-cholesterol (VLDL-C)) and tissues (liver, kidney, heart, and brain). Total cholesterol, triglyceride, free fatty acid, and phospholipid (LDL-C and VLDL-C in plasma only) levels increased in plasma and tissues significantly, whereas plasma HDL-C significantly decreased in diabetic rats. Treatment with 3-HMX or glibenclamide reversed the above-mentioned changes and improved toward normalcy. Histological study of liver also confirmed the biochemical findings. Thus administration of 3-HMX is able to reduce hyperglycemia and hyperlipidemia related to the risk of diabetes mellitus. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:95,101, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20317 [source] Hepatic electrical stimulation reduces blood glucose in diabetic ratsNEUROGASTROENTEROLOGY & MOTILITY, Issue 10 2010J. Chen Abstract Background, The aim of this study was to investigate the feasibility and mechanisms of controlling blood glucose using hepatic electrical stimulation (HES). Methods, The study was performed in regular Sprague-Dawley (SD) rats, streptozotocin-induced type 1 diabetic rats and Zucker diabetic fatty (ZDF) rats chronically implanted with one pair of stimulation electrodes on two lobes of the liver tissues. Key Results, (i) Hepatic electrical stimulation was effective in reducing blood glucose by 27%,31% at time points 60, 75 and 90 min after oral glucose in normal rats; (ii) HES reduced blood glucose in both fasting and fed states in both type 1 and type 2 diabetic rats; (iii) Chronic HES decreased the blood glucose level, and, delayed gastric empty and increased plasma glucagon-like peptide-1 (GLP-1) level; and (iv) No adverse events were noted in any rats during HES. Histopathological analyses and liver function tests revealed no electrode dislodgement, tissue damages or liver enzyme changes with HES. Conclusions & Inferences, Hepatic electrical stimulation is capable of reducing both fasting and fed blood glucose in normal, and type 1 and type 2 diabetic rats and the effect may be partially mediated via an increase in GLP-1 release. [source] Zinc ions in ,-cells of obese, insulin-resistant, and type 2 diabetic rats traced by autometallographyAPMIS, Issue 12 2003L. G. SØNDERGAARD Zinc ions in the secretory granules of ,-cells are known to glue insulin molecules, creating osmotically stable hexamers. When the secretory granules open to the surface, the zinc ion pressure decreases rapidly and pH levels change from acid to physiological, which results in free insulin monomers and zinc ions. The released zinc ions have been suggested to be involved in a paracrine regulation of ,- and ,-cells. Since zinc is intimately involved in insulin metabolism and because zinc homeostasis is known to be disturbed in type 2 diabetes, we decided to study the ultrastructural localisation of zinc ions in insulin-resistant and type 2 diabetic rats as compared to controls. By means of autometallography, the only method available for demonstrating zinc ions at ultrastructural levels, we found zinc ions in the secretory granules and adjacent to the plasma membrane. The membrane-related staining outside the plasma membrane reflects release of zinc ions during exocytosis. No apparent difference was found in the ultrastructural localisation of zinc ions when we compared the obese Zucker (fa/fa) rats, representing the insulin resistance syndrome, and the GK rats, representing type 2 diabetes, with controls. This suggests that the ultrastructural localisation of zinc ions is unaffected by the development of type 2 diabetes in rats in a steady state of glycaemia. [source] Effect of AOB, a fermented-grain food supplement, on oxidative stress in type 2 diabetic ratsBIOFACTORS, Issue 2 2007Yukiko Minamiyama Abstract Reactive oxygen species (ROS) play an important role in the pathogenesis of diabetic complications. Antioxidant Biofactor (AOB) is a mixture of commercially available fermented grain foods and has strong antioxidant activity. This study investigated the effect of AOB supplementation of standard rat food on markers of oxidative stress and inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes. Blood glucose, hemoglobin A1c, plasma free fatty acid, triacylglycerol and plasminogen activator inhibitor-1 (PAI-1) were significantly higher in OLETF rats than in non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats at 29 weeks. AOB (6.5% of diet) was given to rats during 29,33 weeks of diabetic phase in OLETF rats. OLETF rats with AOB supplementation showed decreased blood glucose, hemoglobin A1c, triacylgycerol, low density lipoprotein, cholesterol and PAI-1. Mitochondrial ROS production was significantly increased in heart, aorta, liver and renal artery of OLETF rats. Uncoupling protein 2 (UCP2) is known to regulate ROS production. We found aortic UCP2 protein expression increased in OLETF rats, and AOB returned UCP2 expression to normal. Aortic endothelial NO synthase (eNOS) was also increased in OLETF rats more than in LETO rats at 33 weeks. In contrast, phosphorylated vasodilator-stimulated phosphoprotein, an index of the NO-cGMP pathway, was significantly diminished. AOB increased eNOS proteins in LETO and OLETF rats. In conclusion, AOB significantly improved the NO-cGMP pathway via normalizing ROS generation in OLETF rats. The data suggest that dietary supplementation with AOB contributes to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus. [source] CGS 35601, a Triple Inhibitor of Angiotensin Converting Enzyme, Neutral Endopeptidase and Endothelin Converting EnzymeCARDIOVASCULAR THERAPEUTICS, Issue 4 2005Bruno Battistini ABSTRACT CGS 35601 (L-tryptophan, N-[[1-[[(2S)-2-mercapto-4-methyl-1-oxopentyl]amino]-cyclopentyl]carbonyl]) is one of a few single molecules capable of inhibiting the activities of angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP) and endothelin converting enzyme (ECE) simultaneously, with IC50 values of 22, 2, and 55 nM, respectively. Through the inhibition of ACE and ECE, it blocks the conversion of angiotensin I (AI) and big endothelin-1 (big ET-1) into the two most potent peptidic vasoconstrictors, angiotensin II (AII) and ET-1, respectively. By inhibiting NEP, CGS 35601 also prevents the degradation of peptidic vasodilators such as bradykinin (BK), natriuretic peptides (NPs) and adrenomedullin (ADM) and, hence, modulates the secondary release of other vasoactive mediators such as nitric oxide (NO) and prostaglandins. In chronic (30 days) experiments, CGS 35601 is well tolerated with a very good safety profile in healthy normotensive, hypertensive and type 2 diabetic rats. The antihypertensive efficacy of CGS 35601 was demonstrated in chronically instrumented, unrestrained and conscious rat models of hypertension (SHR and DSS) and type 2 diabetes (ZDF-fatty). It lowered blood pressure effectively as well as modulated plasma concentrations of a number of circulating vasoactive peptidic mediators that are keys to the regulation of the vascular tone. These data suggest that CGS 35601, a triple vasopeptidase inhibitor (VPI), may represent a novel class of antihypertensive drugs and may have the potential to reduce morbidity and mortality from cardiovascular disorders, diabetes and subsequent renal complications. Similar in vivo ACE, NEP, and ECE inhibitory activities were also observed with the orally active prodrug, CGS 37808 (L-tryptophan, N-[[1-[[(2S)-2-(acetylthio)-4-methyl-1-oxopentyl]amino]cyclopentyl]-carbonyl]-, methyl ester. [source] | ||||||||||