Autocrine regulation of glucose metabolism in pancreatic islets

MARÍA I. BORELLI; FLAVIO FRANCINI; JUAN JOSÉ GAGLIARDINO

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

American Physiological Society

Lugar: Bethesda; Año: 2004 vol. 286 p. 111 - 115

0193-1849

We evaluated the possible autocrine modulatory effect of insulin upon glucose metabolism and glucose-induced insulin secretion in islets isolated from normal hamsters. We measured 14CO2 and 3H2O production from D-[U-14C]-glucose and D-[5-3H]-glucose, respectively, in islets incubated with 0.6, 3.3, 8.3, and 16.7 mM glucose alone, or with 5 or 15 mU/ml insulin, anti-insulin guinea-pig serum (1:500), 25 µM nifedipine, or 150 nM wortmannin. Insulin release was measured (radioimmunoassay) in islets incubated with 3.3 or 16.7 mM glucose, with or without 75, 150, and 300 nM wortmannin. Insulin enhanced significantly 14CO2 and 3H2O production with 3.3 mM glucose, but not with 0.6, 8.3 or 16.7 mM glucose. Addition of anti-insulin serum to the medium with 8.3 and 16.7 mM glucose decreased significantly 14CO2 and 3H2O production. A similar decrease was obtained in islets incubated with 8.3 and 16.7 mM glucose and wortmannin or nifedipine. This latter effect was reverted adding 15 mU/ml insulin to the medium. Glucose metabolism was almost abolished when islets were incubated in a Ca2+-deprived medium, but this effect was not reverted by insulin. No changes were found in 14CO2 and 3H2O production by islets incubated with 3.3 mM glucose and anti-insulin serum, wortmannin, or nifedipine in the media. Addition of wortmannin decreased significantly insulin release induced by 16.7 mM glucose in a dose-dependent manner. Our results suggest that insulin exerts a physiological autocrine stimulatory effect upon glucose metabolism in intact islets, as well as on glucose-induced insulin release. Such effect however, depends on the glucose concentration in the incubation medium.