Modulation of metabolic and cardiac dysfunctions by insulin sensitizers and angiotensin receptor blocker in rat model of type 2 diabetes mellitus

Abstract

The objective of this study was to investigate the modulation of metabolic dysfunctions, adiponectin levels, and cardiac dysfunctions of type 2 diabetes mellitus (T2DM) by a combination of the insulin sensitizer rosiglitazone and angiotensin receptor blocker telmisartan in an experimental rat model. Fifty male adult Sprague-Dawley rats were divided equally into 5 groups. Group I: fed normal chow; served as normal control group. Groups II-V: fed a high-fat diet (HFD) for 2 weeks, followed by injection of streptozotocin (STZ; 35 mg/kg) to create a model of T2DM. Group II: treated with vehicle. Group III: treated with rosiglitazone (4 mg/kg). Group IV: treated with telmisartan (5 mg/kg). Group V: treated with both agents. Untreated HFD-STZ rats showed elevated fasting blood glucose, insulin, homeostasis model assessment (HOMA) index, triglycerides (TGs), low-density lipoprotein cholesterol (LDL), and total serum cholesterol (TC), with a decrease in high-density lipoprotein cholesterol (HDL) and adiponectin levels (p < 0.001). Rosiglitazone exerted more improvement in all parameters than telmisartan did, and a combination of both did not augment the improvement further, except for TGs and adiponectin. For the isolated atrial study, a combination of rosiglitazone and telmisartan corrected the responses of the atria of HFD-STZ rats to the negative inotropic effect induced by adenosine better than either one did alone, whereas this combination, surprisingly, significantly attenuated the positive inotropic response to β-adrenoreceptor and α-adrenoreceptor agonists. In conclusion, rosiglitazone significantly improved the metabolic and cardiac dysfunctions in T2DM. Moreover, a combination of rosiglitazone and telmisartan offered more improvement in serum TGs and adiponectin, and restored the atrial inotropic response to adenosine. Surprisingly, this combination significantly attenuates the positive inotropic response to α1-adrenoreceptor and β-adrenoreceptor agonists.

Comparative Study of the Effects of GLP1 Analog and SGLT2 Inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

“…The present study found high blood glucose with relative insulin deficiency and high HOMA-IR in the DM group, indicating T2DM development. Previous studies reported similar findings [18,22,23]. Lack of insulin and hyperglycemia developed in this animal model could be due to partial damage of pancreatic β-cells via the cytotoxic action of STZ and block of insulin receptors by a high-fat diet [22,23].…”

“…The details of induction of Type 2 DM in rats was mentioned in our previous study [18]. Briefly, rats were given a high-fat diet for 4 weeks.…”

Exogenous adiponectin with full Peroxisome proliferator-activated receptor agonists (pioglitazone) abrogates streptozotocin induced oxidative stress and vascular abnormalities in Spontaneously hypertensive rats.

“…Therefore, PPAR-γ agonists used in our study probably in uenced the gene expression responsible for lipid and carbohydrate metabolism without affecting glycaemic levels in diabetic SHRs. To support our observations previous observation proved that pioglitazone attenuated dyslipidemia in cyclosporine induced hypertensive rats (65), whereas, in another study, Hussain proved a much greater bene cial effect of a combination of rosiglitazone and telmisartan offered more improvement in serum TGs and adiponectin (66). Interestingly, treating diabetic rats with exogenous adiponectin and pioglitazone as full PPAR-γ agonist, produced signi cant attenuation of metabolic dysfunctions, as evidenced by the signi cant decrease in TC, TGs, LDL, but an increase in HDL and adiponectin plasma concentrations as similar conclusion were drawn for plasma adiponectin concentration.…”

Autophagy promotion and fibrosis inhibition by combination of GLP1 analogue and metformin decreasing the progression of type II diabetic cardiomyopathy of albino rats: Immunohistochemical study

“…previous study done by [21] we can make a model of type 2 diabetes as each rat received high fat diet for 4 weeks then streptozotocin (STZ) (35 mg/Kg) was injected intraperitoneally. These rats were considered diabetic when rats tail blood sugar > 200 mg/dL after 48 h after injection.…”