Effects of cholinergic agonists on diacylglycerol and intracellular calcium levels in pancreatic beta-cells.
We have studied the effects of cholinergic agonists on the rates of insulin release and the concentrations of diacylglycerol (DAG) and intracellular free Ca2+ ([Ca2+]i) in the beta-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 beta-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 increase 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 beta-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.
Weng
L
L
Nuffield Department of Clinical Biochemistry, John Radcliffe Hospital, Headington, Oxford, U.K.
Davies
M
M
Ashcroft
S J
SJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D004075:Diglycerides / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009116:Muscarine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010277:Parasympathomimetics / Q000378:metabolism*; D013997:Time Factors
D004075:Diglycerides; D007328:Insulin; D010277:Parasympathomimetics; D009116:Muscarine; D002217:Carbachol; D005947:Glucose; D000109:Acetylcholine; D001839:Bombesin; D002118:Calcium