Influence of monooleoylglycerol on islet cell phosphoinositide hydrolysis and insulin secretion

The diacylglycerol kinase inhibitor monooleoylglycerol (MOG) produced a dose-dependent increase in both phosphoinositide (PI) hydrolysis and insulin secretion in the presence of a substimulatory glucose level (2.75 mM). This effect could not be reproduced by the combination of oleic acid plus glycerol, potential metabolic products derived from MOG catabolism. At a level (25 microM) which has no significant effect on beta cell insulin secretion or PI hydrolysis in the presence of 2.75 mM glucose, MOG significantly potentiated the insulin stimulatory effect of the sulfonylurea tolbutamide (200 microM) in the presence of 7 mM glucose. This heightened insulin secretory response and PI hydrolysis were effectively attenuated by the calcium channel blocker nitrendipine (0.5 microM). These findings indicate that MOG has complex effects on beta cell performance. It promises, however, to be a useful probe in assessing how events associated with increases in PI hydrolysis influence insulin secretion.