β₂-adrenoceptor and insulin receptor expression in the skeletal muscle of streptozotocin induced diabetic rats: antagonism by vitamin D₃ and curcumin.

Diabetes mellitus is a heterogeneous disease and nutritional therapy forms a necessary dimension for its long-term management. Traditional medicinal plants and vitamins are the potentially useful natural products for diabetes control. Diabetes causes atrophy and wasting of skeletal muscles resulting in major peripheral damage. The current study was designed to investigate the therapeutic effect of vitamin D₃ and curcumin treatment on β₂-adrenoceptors, transcription factor CREB, insulin receptors, protein kinase B (Akt) and malate dehydrogenase activity in the skeletal muscle of diabetic rats. Radioreceptor binding assay was done for β₂-adrenoceptors using specific ligand, [³H] propranolol and gene expression studies of β₂-adrenoceptors, transcription factor CREB, insulin receptors and Akt were also done using specific probes. The results of the β₂-adrenoceptor assay showed significant increase in binding parameters, receptor number (B(max)) and equilibrium dissociation constant (K(d)) in the diabetic group in comparison to control. Similarly, an up regulation of β₂-adrenoceptor and CREB gene expression was observed in the diabetic group whereas the insulin receptor expression was down regulated which signifies the increased glycogenolysis, gluconeogenesis and decreased glycogenesis in the muscles. Expression of Akt was found to be up regulated in the diabetic group. Malate dehydrogenase activity was significantly decreased in both cytosolic and mitochondrial fractions of the diabetic group. All these molecular aspects were reversed to near control with vitamin D₃ and curcumin treatment. Our results suggest the rising potential of both vitamin D₃ and curcumin in the management of peripheral complications associated with diabetes.