Effects of cholinergic agonists on diacylglycerol and intracellular calcium levels in pancreatic β-cells |
| |
Authors: | Ling Weng Mark Davies Stephen JH Ashcroft |
| |
Institution: | Nuffield Department of Clinical Biochemistry, John Radcliffe Hospital, Headington, Oxford OX3 9DU, U.K. |
| |
Abstract: | We have studied the effects of cholinegic agonists on the rates of insulin release and the concentrations of diacylglycerol (DAG) and intracellular free Ca2+ (Ca2+]i) in the β-cell line MIN6. Insulin secretion was stimulated by glucose, by glibenclamide and by bombesin. In the presence of glucose, both acetylcholine (ACh) and carbachol (CCh) produced a sustained increase in the rate of insulin release which was blocked by EGTA or verapamil. The DAG content of MIN6 β-cells was not affected by glucose. Both CCh and ACh evoked an increase in DAG which was maximal after 5 min and returned to basal after 30 min; EGTA abolished the cholinergic-induced increased in DAG. ACh caused a transient rise in Ca2+]i which was abolished by omission of Ca2+ or by addition of devapamil. Thus, cholinergic stimulation of β-cell insulin release is associated with changes in both Ca2+]i and DAG. The latter change persists longer than the former and activation of protein kinase C and sensitization of the secretory process to Ca2+ may underlie the prolonged effects of cholinergic agonists on insulin release. However, a secretory response to CCh was still evident after both Ca2+]i and DAG had returned to control values suggesting that additional mechanisms may be involved. |
| |
Keywords: | Insulin release acetylcholine diacylglycerol intracellular calcium β-cell |
本文献已被 ScienceDirect 等数据库收录! |