Vitamin D3 restores altered cholinergic and insulin receptor expression in the cerebral cortex and muscarinic M3 receptor expression in pancreatic islets of streptozotocin induced diabetic rats.
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.
Kumar
Peeyush T
PT
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Cochin, Kerala 682 022, India.
Antony
Sherin
S
Nandhu
Mohan S
MS
Sadanandan
Jayanarayanan
J
Naijil
George
G
Paulose
Chiramadathikudiyil S
CS
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002762:Cholecalciferol / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000178:diet therapy* / Q000378:metabolism; D015870:Gene Expression; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism*; D043643:Receptor, Muscarinic M1 / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism; D013311:Streptozocin; D064569:alpha7 Nicotinic Acetylcholine Receptor
D001786:Blood Glucose; C579165:Chrna7 protein, rat; D051274:Glucose Transporter Type 3; D007328:Insulin; D018696:Neuroprotective Agents; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D011978:Receptors, Nicotinic; C495690:Slc2a3 protein, rat; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002762:Cholecalciferol; D013311:Streptozocin; D011972:Receptor, Insulin; D000110:Acetylcholinesterase