Abstract
In the present study, we have investigated acetylcholine esterase (AChE) activity and muscarinic M 1, M 3 receptors kinetics in the brainstem of both young and old streptozotocin induced and insulin treated diabetic rats (D + I). Also, the functional role of acetylcholine and muscarinic receptors in insulin secretion from the pancreatic islets was studied in vitro. 90 week old control rats showed decreased V max ( P < 0.001) for AChE compared to 7 week old control rats. V max was decreased ( P < 0.001) in 7 week diabetic groups whereas 90 week old diabetic groups showed increased ( P < 0.001) V max when compared to their respective controls. Binding studies using [ 3H]QNB and [ 3H]DAMP of 90 week old control showed significant increase in the B max ( P < 0.001) and K d ( P < 0.01) of muscarinic M 1 receptors whereas M 3 receptor number was decreased significantly ( P < 0.001) with no change in affinity when compared to 7 week old control respectively. M 1 receptor number was decreased significantly ( P < 0.001) whereas M 3 receptor number was increased significantly ( P < 0.001) in both 7 week and 90 week old diabetic rat groups compared to their respective controls. The competition curve for [ 3H]QNB fitted for two sited model in 7 week old groups whereas fitted for one sited model in 90 week old groups. [ 3H]DAMP was fitted for two sited model in both 7 week and 90 week old groups. Insulin treatment significantly reversed ( P < 0.001) the binding parameters to near control level. In vitro studies showed that acetylcholine through muscarinic M 1 and M 3 receptors stimulated insulin secretion from the pancreatic islets. Thus our studies suggest that both brainstem and pancreatic muscarinic M 1, M 3 receptors differentially regulate the cholinergic activity and insulin secretion which will have clinical significance in the management of diabetes and insulin treatment as a function of age.
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