ABSTRACT
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 ß2-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 ß2-adrenoceptors using specific ligand, [³H] propranolol and gene expression studies of ß2-adrenoceptors, transcription factor CREB, insulin receptors and Akt were also done using specific probes. The results of the ß2-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 ß2-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.
Subject(s)
Cholecalciferol/pharmacology , Curcumin/pharmacology , Diabetes Mellitus, Experimental/metabolism , Muscle, Skeletal/metabolism , Receptor, Insulin/genetics , Receptors, Adrenergic, beta-2/genetics , Animals , Blood Glucose/analysis , Cyclic AMP Response Element-Binding Protein/genetics , Diabetes Mellitus, Experimental/blood , Gene Expression Regulation/drug effects , Insulin/blood , Malate Dehydrogenase/metabolism , Male , Muscle, Skeletal/drug effects , Proto-Oncogene Proteins c-akt/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , StreptozocinABSTRACT
OBJECTIVE: In the present study, we investigated the alteration of gamma-aminobutyric acid A (GABAA) receptors in the hypothalamus of rats during pancreatic regeneration. METHODS: Three groups of rats were used for the study: sham operated, 72 hours partially pancreatectomized, and 7 days partially pancreatectomized. The GABA receptor assay was performed by using the [H]GABA as ligand to the Triton X-100-treated membranes, and displacement with unlabeled GABA and [H]bicuculline binding to the GABAA receptors was assayed in Triton X-100-treated synaptic membranes and displacement with unlabeled bicuculline. RESULTS: The GABA content in the brain regions and pancreas of the sham and experimental rat groups was quantified by displacement method. In the hypothalamus, the high-affinity GABAA receptor binding showed a significant decrease in maximal binding (P < 0.01) and equilibrium dissociation constant (P < 0.05) in 72 hours and 7 days partially pancreatectomized rats. The content of GABA has significantly decreased in the hypothalamus during the regeneration of pancreas. CONCLUSIONS: This effect of GABAA receptors in hypothalamus suggests a regulatory role during active regeneration of pancreas that will have significance in insulin secretion.
