Atorvastatin prevents type 2 diabetes mellitus—An experimental study (original) (raw)
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Effects of atorvastatin on glucose metabolism and insulin resistance in KK/Ay mice
Journal of atherosclerosis and thrombosis, 2005
Insulin resistance plays an important role not only in the development and progression of diabetes mellitus but also in the establishment of metabolic syndrome. Improvement of insulin resistance is thus of great importance both in improving glucose metabolism and preventing atherosclerosis. Although HMG-CoA reductase inhibitors appear to favorably affect glucose metabolism, as indicated by the results of a subanalysis in the West of Scotland Coronary Prevention Study (WOSCOPS), their effects on glucose metabolism and insulin resistance have not been thoroughly investigated in animal models. In this study, the effects of atorvastatin on the glucose metabolism and insulin resistance of KK/Ay mice, an animal model of type II diabetes, were investigated. Atorvastatin significantly decreased the non-HDL-cholesterol level in the oral glucose tolerance test, inhibited increase in the 30-min glucose level, decreased plasma insulin levels before and 30 and 60 minutes after glucose loading, a...
International Journal of Basic & Clinical Pharmacology, 2017
Background: Dyslipidemia and glucose intolerance are closely associated with each other especially as a part of metabolic syndrome. Statins are the drug of choice for treatment of dyslipidemia and for primary prevention of coronary heart disease in diabetics. Recent studies indicate risk of new onset diabetes in patients receiving statins. Hence it was worthwhile to study the effect of two most commonly used statins, which differ in their lipophilicity, on glucose tolerance in prediabetic animal model.Methods: The study consisted of 3 groups with 6 wistar rats in each and hyperglycemia was induced by intraperitoneal injection of low dose (25mg/kg) streptozotocin. Group 1 served as control, group 2 and 3 were given Atorvastatin and Rosuvastatin respectively for 8 weeks. Oral glucose tolerance test (OGTT) was performed at 0,1 and 2 hrs after glucose load on days 0, 14, 28, 42 and 56 days.Results: Starting from 28th day onwards both the treatment groups showed progressive worsening of ...
Diabetologia, 2005
Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that are being extensively used for the treatment of hypercholesterolaemia in clinical practice. Competitive inhibition of HMG-CoA reductase by statins reduces, apart from cholesterol, the synthesis of isoprenoid intermediates, such as dolichol, ubiquinone, farnesol and geranylgeraniol, which are involved in posttranslational protein modification. This impairment of isoprenoid synthesis has been suggested to form the basis for the pleiotropic effects of statins, which include their anti
European Journal of Pharmacology, 2007
We investigated whether atorvastatin, given in a dose to low to influence the lipid profile, has any effect on oxidative stress, inflammation and endothelial function under streptozotocin-induced diabetic conditions. Diabetes mellitus was induced in male Sprague Dawley rats by a single injection of streptozotocin. Rats were treated chronically with atorvastatin (50 mg/kg/day; p.o.) or vehicle until day 48 and compared with controls. NAD(P)H activity, protein expression nuclear factor-κBp65 (NF-κBp65) and phosphorylation of the extracellular signal-regulated kinase (ERK1/2) were assessed in the quadriceps muscle. Protein and mRNA levels of intracellular and vascular adhesion molecules (ICAM-1, VCAM-1) and cytokines were measured by Taqman or immunohistochemistry staining, respectively. Endothelial function was investigated in vivo using the autoperfused hind limb model. Diabetic groups displayed similar severe hyperglycemia. Untreated diabetic rats showed enhanced NAD(P)H activity, activation of the ERK1/2/NF-κBp65-pathway, enhanced expression of cytokines and cellular adhesion molecules and impaired vascular function. Low-dose therapy by atorvastatin did not alter the lipid profile but led to a reduction of NAD(P)H activity (− 28%, P b 0.05) associated with reduced protein expression of NF-κBp65 (− 53%, P b 0.05) and phosphorylation of its regulator mitogen-activated protein kinase (MAPK) ERK1/2 in diabetic rats. Also inflammatory markers were reduced after atorvastatin treatment indexed by reduced mRNA expression of VCAM-1 (−24%), tumor necrosis factor α (− 59%) and interleukin 1β (−50%) and reduced ICAM-1 (−81%) and VCAM-1 (−74%) positive staining. These beneficial effects were associated with improved endothelium-dependent vasodilatation (maximal vasodilatation: +101%; P b 0.05). Lipid-independent antioxidative and anti-inflammatory effects of low-dose atorvastatin involving the ERK1/2/NF-κB-pathway are sufficient to improve endothelial function under experimental diabetic conditions.
Archives of Pharmacal Research, 2012
We investigated the possible protective effect of atorvastatin against vascular dysfunction associated with insulin resistance (IR) in fructose-fed model rats. The effect of atorvastatin (10 mg/kg/day for 8 weeks) on vascular reactivity, glucose, cholesterol, insulin, and the IR index in a well-established model of dietary hypertriglyceridemia, the fructose-fed rat, was investigated. Fructose feeding (10% fructose in drinking water for 8 weeks) induced hypercholesterolemia and hyperinsulinemia without any change in blood glucose levels. Fructose feeding also elevated serum tumor necrosis factor-alpha (TNF-α), the insulin resistance index, leukocyte infiltration, and endothelial cell pyknosis. Fructose feeding induced hyper-responsiveness to both phenylephrine (PE), KCl, and hyporesponsiveness to acetylcholine (Ach) but not to sodium nitroprusside-induced relaxation. Atorvastatin, given concurrently with fructose, reduced hypercholesterolemia, hyperinsulinemia, TNF-α level, and the IR index. It also reduced leukocyte infiltration and endothelial cell pyknosis and decreased hyper-responsiveness to both PE and KCl but did not affect hyporesponsiveness to Ach relaxation. In conclusion, atorvastatin protected against impairment in aortic vascular reactivity associated with insulin resistance, particularly increased contractility, but not reduced endothelium-dependent relaxation, by a mechanism involving a reduction in cholesterol and IR in addition to anti-inflammatory effects.
Journal of Biochemical and Molecular Toxicology, 2019
In the present study, we investigate the effects of atorvastatin on the lipid profile, oxidative stress, and liver enzyme markers, and its protective activity against diabetic complications, in streptozotocin (STZ)-induced diabetic rats. Fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and high-density lipoprotein (HDL) levels, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme activities, were measured 7 weeks after the administration of STZ and atorvastatin. Thiobarbituric acid reactive substances (TBARS), non-protein associated sulfhydryl (NP-SH), total sulfhydryl (T-SH), and nitric oxide (NO) levels were measured to evaluate oxidative stress. Atorvastatin was found to inhibit ALT and AST activities and to reduce FBG levels in rats with STZ-induced diabetes. Moreover, atorvastatin treatment significantly reduced lipid peroxidation in kidney, heart, and eye tissues (P < 0.001, for all), and resulted in a significant increase in NP-SH levels in brain tissues (P < 0.001). Total NO and nitrate levels increased significantly after atorvastatin treatment (P < 0.01). Our results revealed that atorvastatin has a protective effect against STZ-induced oxidative damage by reducing TBARS levels and increasing NP-SH levels, has a hepatoprotective effect by decreasing ALT and AST activities. It also shows the antihyperglycemic activity by lowering FBG levels.
International Journal of Medical Laboratory
Background and Aims: Atorvastatin may alter glycemic traits and lipid profiles. This study aimed to evaluate the effects of atorvastatin on biochemical variables in patients with type 2 diabetes and pre-diabetes (borderline diabetes). Materials and Methods: This study included 80 individuals divided into five groups. Patients with type 2 diabetes mellitus and pre-diabetes used atorvastatin 20 mg/day for three months. After three months, variables such as serum fasting blood glucose (FBS), cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and glycosylated hemoglobin (HbA1c) levels were measured to assess the status of diabetes and pre-diabetes condition. Linear regression was applied to determine the association between atorvastatin uses and alters of biochemical variables levels. Results: The serum FBS and HbA1c levels in patients with diabetes and pre-diabetes who use atorvastatin were significantly lower than in p...
Advances in Human Biology, 2021
Objective: The induction of type II diabetes mellitus (T2DM) rat model using the Sprague Dawley (SD) species is commonly performed for further laboratory experimental purposes. Various laboratory conditions or even other environments provide different outcomes in achieving the model utilising the previous protocol. Materials and Methods: We performed an experimental animal study. Researchers administered a revamped induction regimen involving a variation of a high-fat diet (HFD) with several low-dose streptozotocin injections and a glucose drink immediately after injection. Results: HFD-fed rats have demonstrated severe hyperglycaemic status, though they were further evaluated to assess their insulin sensitivity. Analysing subgroups, HFD with glucose drink indicated poor insulin sensitivity after 2 h of intraperitoneal insulin injection. Poor glucose clearance revealed insulin resistance in the rat model (P = 0.026). Different dietary courses and fasting blood glucose were found not significant, P < 0.05. Complementary glucose in HFD was much more likely to cause hyperglycaemic characteristic, although HFD alone did not indicate many discrepancies in hyperglycaemic condition χ2 (2, N = 216) =181.385, P < 0.01. The extra glucose in HFD greatly decreased glucose clearance efficiency, although HFD alone did not demonstrate a clear correlation with the glucose clearance rate, χ2 (2, N = 1003) =700.638, P < 0.01. In addition, the hyperglycaemic state was conversely correlated with insulin sensitivity (r = −0.727, P < 0.001). Conclusion: This approach provides an alternative T2DM induction technique in SD rats. The key features of T2DM, including hyperglycaemic state and insulin insensitivity, were successfully developed in the animal model.
Atorvastatin induces insulin sensitization in Zucker lean and fatty rats
Atherosclerosis, 2006
The 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors ('statins') have been implicated in preventing new onset type 2 diabetes, whereas the mechanism of this effect is not known. We investigated the effects of an HMG-CoA reductase inhibitor, atorvastatin, on insulin sensitization in Zucker lean and fatty rats. Methods and results: In vivo studies of insulin sensitization were performed in chow fed Zucker lean and fatty rats treated with atorvastatin 50 mg/kg/day (ATORVA 50) and results were compared to Zucker lean and fatty rats treated with drug vehicle only (CONT). Additional Zucker lean rats were treated with an intermediate dose of atorvastatin 25 mg/kg/day (ATORVA 25). Treatment with atorvastatin resulted in a dose-dependent improvement in whole body insulin sensitivity in both lean and fatty rats, with an approximately two-fold increase in glucose infusion rate and glucose disposal (Rd) in ATORVA 50 versus CONT (p < 0.01). Atorvastatin 50 mg/kg/day resulted in an increase in 2-deoxyglucose (2-DOG) uptake by skeletal muscles (approximately two-fold increase in 2-DOG uptake in quadriceps (p = 0.06) and gastrocnemius (p < 0.01)) in lean Zucker rats. Insulin-stimulated phosphorylation of Akt/PKB was significantly increased in skeletal muscle of ATORVA 50 versus CONT in both lean and fatty rats. Conclusion: Atorvastatin induces insulin sensitization in Zucker lean and fatty rats. This may be a clinically important pleiotropic effect if confirmed in insulin resistant humans.