Role of glucose metabolism and phosphoinositide hydrolysis in glucose-induced sensitization/desensitization of insulin secretion from mouse pancreatic islets.
The role of glucose metabolism and phosphoinositide hydrolysis in glucose-induced sensitization/desensitization of insulin secretion was studied. A change in glucose concentration from 5.5 to 16.7 mM during 22-24 h of pre-exposure of mouse islets in TCM 199 culture medium (0.26 mM Ca2+) led to sensitization of glucose-induced insulin secretion. This change in islet responsiveness to glucose was not mediated by increases in glucose utilization ([5-3H]glucose conversion to 3H2O) and glucose oxidation ([U-14C]glucose oxidation to 14CO2). Glucose-induced sensitization of insulin secretion was associated with an increase in glucose-induced phosphoinositide hydrolysis, leading to a significant increase in inositol 1-monophosphate formation, but not in inositol 1,4-bisphosphate or in inositol 1,4,5-trisphosphate plus inositol 1,3,4-trisphosphate formation. Diacylglycerol, which may arise from both phosphoinositide hydrolysis and de novo from glucose metabolism, was, on the other hand, not increased during acute exposure to glucose and not changed after pre-exposure to glucose. At 16.7 mM glucose in TCM 199 medium, a change in Ca2+ concentration from 0.26 to 1.26 mM led to a reduction in glucose-induced insulin secretion. This Ca(2+)-dependent desensitization of insulin secretion in the presence of glucose was associated with a decrease in glucose-induced phosphoinositide hydrolysis, but not with a change in glucose metabolism or diacylglycerol accumulation. In conclusion, it is suggested that glucose-induced sensitization/desensitization of insulin secretion may involve changes in phosphoinositide hydrolysis, but may occur independently of concomitant changes in glucose metabolism or diacylglycerol accumulation.
Thams
P
P
Department of Medical Biochemistry & Genetics, Panum Institute, University of Copenhagen, Denmark.
Hansen
S E
SE
Capito
K
K
Hedeskov
C J
CJ
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003470:Culture Media; D004075:Diglycerides / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006868:Hydrolysis; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010716:Phosphatidylinositols / Q000378:metabolism*
D003470:Culture Media; D004075:Diglycerides; D007328:Insulin; D010716:Phosphatidylinositols; D005947:Glucose; D002118:Calcium