Article

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

Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt.
Canadian Journal of Physiology and Pharmacology (Impact Factor: 1.56). 03/2011; 89(3):216-26. DOI: 10.1139/Y11-012
Source: PubMed

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.

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