THE EFFECTIVENESS OF BETA ADRENOCEPTOR ANTAGONISTS ON PROGRESSION OF INSULIN RESISTANCE AND TYPE 2 DIABETES IN HIGH FAT DIET-FED RATS

The effects of carvedilol, a third generation β-blocker, on progression of insulin resistance and type 2 diabetes mellitus were compared to the prototypic non-selective β-blocker. propranolol. Male albino rats were fed a high fat diet (HFD) for 3 months to induce insulin resistance and mild type 2 diabetes (T2DM). Oral administration of carvedilol (2 or 20 mg/kg), propranolol (30 mg/kg), or vehicle was started along with HFD in different groups. Indices of body composition and insulin resistance, oral glucose tolerance, fasting serum insulin levels, lipid profile, serum levels of lipid peroxidation markers as well as levels of advanced glycosylation end products were determined. In high fat-fed animals, an increase in body composition index, area under the oral glucose tolerance curve, fasting serum insulin, and insulin resistance were observed in comparison to normal diet controls. In addition, significant dyslipidemic changes were also observed in these animals. Moreover, in concordance with these hyperglycemic and dyslipidemic changes, HFD significantly increased serum levels of markers of lipid peroxidation and advanced glycosylation end products (AGEs). On the other hand, β-adrenergic blockers treatment showed better effects on glucose disposal, insulin levels, and insulin resistance. However, carvedilol treatments showed enhanced lipid profiles and lower AGEs when compared to propranolol treatment in HFD animals. These preferential metabolic effects of carvedilol can be attributed to its antioxidant effects and negative regulation of lipolysis. We concluded that carvedilol have protective effects against the development of insulin resistance and T2DM, in addition to amelioration of the consequent cardiovascular complications.