Autocrine regulation of glucose metabolism in pancreatic islets

GAGLIARDINO JJ; BORELLI MI; FRANCINI F

Paris

Congreso; 18th Congress of the International Diabetes Federation; 2003

Background and Aims: It has been recently demonstrated that insulin stimulates in the islets the transcription of glucokinase and insulin genes, Ca2+ flux from endoplasmic reticulum, and exocytosis of insulin. In order to explore further the possible autocrine modulatory effect of insulin upon islet functions, we have studied its effect upon glucose metabolism in islets isolated from pancreases of normal hamsters. Materials and Methods: We measured the production of 14CO2 and 3H2O from D-[U-14C]-glucose and D-[5-3H]-glucose, respectively, in isolated islets (collagenase digestion) incubated with: a) 3.3 mM glucose alone, or plus addition of 5mU/ml insulin; b) 16.7 mM glucose alone, or with the alternative addition of 15 mU/ml insulin, insulin antibody (1:500), normal guinea-pig serum (1:500), 150 nM wortmannin, or 10 ìM nifedipine. Insulin release was also measured (radioimmunoassay) in islets incubated with 3.3 or 16.7 mM glucose, with or without the addition of wortmannin (75, 150 and 300 nM). Results: Insulin enhanced significantly 14CO2 and 3H2O production with 3.3 mM (p<0.001), but not with 16.7 mM glucose. Addition of insulin antibody to the incubation media with 16.7 mM glucose decreased significantly both 14CO2 and 3H2O production (p<0.02). A similar decrease was obtained when the islets were incubated with 16.7 mM glucose and wortmannin (p<0.01) or nifedipine (p<0.01). This latter effect was reverted by addition of 15mU/ml insulin to the incubation media (p<0.01). Addition of wortmannin decreased significantly the amount of insulin released in response to 16.7 mM glucose in a dose-dependent manner (p<0.001). Wortmannin induced a comparable decrease of glucose metabolism and insulin secretion. Conclusion: Our results suggest that insulin exerts a physiological autocrine stimulatory effect upon glucose metabolism (oxidation and utilization) in intact islets, as well as on glucose-induced insulin release.