ABSTRACT
Nutritional therapy is a challenging but necessary dimension in the management of diabetes and neurodegenerative changes associated with it. The study evaluates the effect of vitamin D(3) in preventing the altered function of cholinergic, insulin receptors and GLUT3 in the cerebral cortex of diabetic rats. Muscarinic M3 acetylcholine receptors in pancreas control insulin secretion. Vitamin D(3) treatment in M3 receptor regulation in the pancreatic islets was also studied. Radioreceptor binding assays and gene expression was done in the cerebral cortex of male Wistar rats. Immunocytochemistry of muscarinic M3 receptor was studied in the pancreatic islets using specific antibodies. Y-maze was used to evaluate the exploratory and spatial memory. Diabetes induced a decrease in muscarinic M1, insulin and vitamin D receptor expression and an increase in muscarinic M3, α7 nicotinic acetylcholine receptor, acetylcholine esterase and GLUT3 expression. Vitamin D(3) and insulin treatment reversed diabetes-induced alterations to near control. Diabetic rats showed a decreased Y-maze performance while vitamin D(3) supplementation improved the behavioural deficit. In conclusion, vitamin D(3) shows a potential therapeutic effect in normalizing diabetes-induced alterations in cholinergic, insulin and vitamin D receptor and maintains a normal glucose transport and utilisation in the cortex. In addition vitamin D(3) modulated muscarinic M3 receptors activity in pancreas and plays a pivotal role in controlling insulin secretion. Hence our findings proved, vitamin D(3) supplementation as a potential nutritional therapy in ameliorating diabetes mediated cortical dysfunctions and suggest an interaction between vitamin D(3) and muscarinic M3 receptors in regulating insulin secretion from pancreas.
Subject(s)
Cerebral Cortex/drug effects , Cholecalciferol/pharmacology , Diabetes Mellitus, Experimental/diet therapy , Islets of Langerhans/drug effects , Receptor, Insulin/metabolism , Receptor, Muscarinic M3/metabolism , Acetylcholinesterase/metabolism , Animals , Blood Glucose/analysis , Cerebral Cortex/metabolism , Diabetes Mellitus, Experimental/metabolism , Gene Expression , Glucose Transporter Type 3/metabolism , Insulin/blood , Islets of Langerhans/metabolism , Male , Neuroprotective Agents/pharmacology , Rats , Rats, Wistar , Receptor, Muscarinic M1/metabolism , Receptors, Nicotinic/metabolism , Streptozocin , alpha7 Nicotinic Acetylcholine ReceptorABSTRACT
OBJECTIVES: In this study we have investigated muscarinic M1, M3 receptor kinetics and the functional role of IP3 and cGMP in the corpus striatum of both young and old diabetic and insulin-treated diabetic rats. METHODS: Radioreceptor binding assays was done in the corpus striatum using specific antagonists QNB and DAMP. IP3 and cGMP assay using [3H]IP3 and [3H]cGMP Biotrak assay system kits. KEY FINDINGS: M1 receptor increased and M3 receptor decreased in control old rats when compared with young control rats. In young diabetic groups M1 receptor increased and M3 receptor decreased. Old diabetic groups showed reversed M1 and M3 receptors compared with their controls. IP3 and cGMP content increased in old control rats compared with young control rats. IP3 content increased in young diabetic rats and decreased in old diabetic rats. cGMP content was increased significantly in both young and old diabetic groups. Insulin treatment reversed these altered parameters near to control. CONCLUSIONS: Our studies showed that M1 and M3 receptors, IP3 and cGMP were functionally regulated during diabetes as function of age, which will have immense clinical significance.
Subject(s)
Corpus Striatum/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/drug therapy , Insulin/therapeutic use , Receptor, Muscarinic M1/metabolism , Receptor, Muscarinic M3/metabolism , Age Factors , Animals , Blood Glucose/metabolism , Body Weight/drug effects , Carrier Proteins/metabolism , Diabetes Mellitus, Type 2/metabolism , Inositol 1,4,5-Trisphosphate/metabolism , Insulin/administration & dosage , Intracellular Signaling Peptides and Proteins/metabolism , Male , Rats , Rats, Wistar , StreptozocinABSTRACT
In the present study, serotonin 2C (5-HT(2C)) receptor binding parameters in the brainstem and cerebral cortex were investigated during liver generation after partial hepatectomy (PH) and N-nitrosodiethylamine (NDEA) induced hepatic neoplasia in male Wistar rats. The serotonin content increased significantly (p<0.01) in the cerebral cortex after PH and in NDEA induced hepatic neoplasia. Brain stem serotonin content increased significantly (p<0.05) after PH and (p<0.001) in NDEA induced hepatic neoplasia. The number and affinity of the 5-HT(2C) receptors in the crude synaptic membrane preparations of the brain stem showed a significant (p<0.001) increase after PH and in NDEA induced hepatic neoplasia. The number and affinity of 5-HT(2C) receptors increased significantly (p<0.001) in NDEA induced hepatic neoplasia in the crude synaptic membrane preparations of the cerebral cortex. There was a significant (p<0.01) increase in plasma norepinephrine in PH and (p<0.001) in NDEA induced hepatic neoplasia, indicating sympathetic stimulation. Thus, our results suggest that during active hepatocyte proliferation 5-HT(2C) receptor in the brain stem and cerebral cortex are up-regulated which in turn induce hepatocyte proliferation mediated through sympathetic stimulation.
