Alpha1-adrenergic receptor blocking action of carvedilol contributes to tackling dexamethasone-induced insulin resistance and to a lesser extent hepatic damage

Insulin resistance is a well-established risk factor for serious health problems, including type 2 diabetes, cardiovascular disease, and stroke. Carvedilol has been documented to improve insulin sensitivity, ameliorate hyperlipidemia, and reduce the risk of diabetes. This study aimed to explore the role of α1-adrenergic receptors (α1ARs) in mediating the insulin-sensitizing effect of carvedilol in dexamethasone-treated rats. Insulin resistance was induced by subcutaneous injection of dexamethasone (10 mg/kg) for 7 days in rats. Five groups were used: control; dexamethasone; carvedilol (10 mg/kg); phenylephrine (1 mg/kg); carvedilol and phenylephrine. Serum glucose, insulin, and lipid profiles, as well as hepatic glycogen content, diacylglycerol level, protein kinase B activity, collagen type I, histopathological changes, and β-arrestin2 immunohistochemistry, were measured. The results demonstrated that blocking of α1- and β-ARs by carvedilol mitigated dexamethasone-induced insulin resistance and hepatic damage. Moreover, pre-injection of phenylephrine attenuated the insulin-sensitizing effect of carvedilol and, to a lesser extent, hepatic damage. In conclusion, the α1-blocking action of carvedilol contributes to its insulin-sensitizing effect as well as to its beneficial effect on the lipid profile. On the other hand, the hepatoprotective effect of carvedilol in dexamethasone-treated rats is less dependent on the α1AR.