Influence of staurosporine, nitrendipine and monooleoylglycerol on interleukin-1-induced insulin secretion and phosphoinositide hydrolysis.
The monokine interleukin-1 alpha (IL-1) induces a glucose-dependent increase in insulin secretion, an effect tentatively attributed to its ability to increase beta cell phosphoinositide (PI) hydrolysis. In the present experiments, the effects of the protein kinase C inhibitor staurosporine (20 nM), the calcium channel antagonist nitrendipine (5 microM), and the diacylglycerol kinase inhibitor monooleoylglycerol (MOG, 25 microM) on 40 nM IL-1-induced increments in insulin release from perifused islets and inositol phosphate levels in [3H]inositol prelabeled islets were assessed. In perifused islets, insulin secretion in response to IL-1 in the presence of 7 mM glucose averaged 313 +/- 43 pg/islet/min 35-40 min after the onset of stimulation. Release from control islets perifused in the presence of 7 mM glucose alone averaged 56 +/- 6 pg/islet/min at this time point. The addition of staurosporine together with IL-1 reduced insulin secretion at this time point to 88 +/- 21 pg/islet/min. This level of IL-1 caused significant increases in inositol phosphate accumulation in the presence of 7 mM glucose but not 2.75 mM glucose. Staurosporine was without a significant effect on inositol phosphate accumulation in response to the monokine. In contrast, nitrendipine (5 microM) inhibited insulin release and inositol phosphate accumulation in a parallel fashion. Finally, MOG significantly amplified release to the monokine without significantly affecting its impact on inositol phosphate accumulation. Nitrendipine or staurosporine blocked this amplifying effect of MOG on secretion. These results emphasize the role of PI hydrolysis in IL-1-induced insulin secretion and suggest further that calcium influx is essential for IL-1 to fully activate both PI hydrolysis and insulin secretion.
Zawalich
W S
WS
Yale University School of Nursing, New Haven, CT 06536-0740.
Zawalich
K C
KC
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D005989:Glycerides / Q000494:pharmacology*; D006868:Hydrolysis; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000502:physiology*; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine
D000470:Alkaloids; D005989:Glycerides; D007328:Insulin; D007375:Interleukin-1; D010716:Phosphatidylinositols; D009568:Nitrendipine; C005953:monoolein; D019311:Staurosporine