Pancreatic islets: a new target for insulin resistance?

FRANCINI F; BORELLI MI; GAGLIARDINO JJ

Helsingor, Dinamarca

Workshop; EASD Islet Study Group Symposium 2006. Beta cell replacement/regeneration in diabetes therapy; 2006

European Association for the Study of Diabetes

Aim: To evaluate the autocrine modulatory effect of insulin on glucose metabolism and glucose-induced insulin secretion in islets isolated from normal control hamsters and from hamsters with insulin resistance induced by the administration of a sucrose-rich diet (SRD). Material and Methods: We measured 14CO2 and 3H2O production from D-[U-14C]-glucose and D-[5-3H]-glucose, respectively, in islets incubated with 3.3 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 by radioimmunoassay in islets incubated with 3.3 or 16.7 mM glucose, with or without 75, 150, and 300 nM wortmannin. Results: Insulin enhanced 14CO2 and 3H2O production in control islets, but this effect was significantly decreased or absent in SRD islets. Whereas addition of anti-insulin serum, nifedipine or wortmannin to the medium with 16.7 mM glucose decreased significantly 14CO2 and 3H2O production in control islets, such effect was not observed in SRD islets. Addition of wortmannin did not decrease significantly insulin release induced by 16.7 mM glucose in SRD hamsters, but it did in controls. Conclusions: Our results show that the physiological autocrine stimulatory effect of insulin on glucose metabolism observed in intact normal islets is attenuated or even absent in islets from animals with a dietary-induced insulin resistance.