Decreased islet sensitivity to insulin in hamsters with dietary-induced insulin resistance

FRANCINI F; GAGLIARDINO JJ; BORELLI MI

Life Sciences

Año: 2008 vol. 82 p. 817 - 822

The aim of this study was to evaluate the autocrine modulatory effect of insulin on glucose metabolism and glucose-induced insulin secretion in islets isolated from hamsters with insulin resistance induced by administration of a sucrose-rich diet (SRD) during 5 weeks. For this pourpose we use a two-metabolic-pathways approach (glucose oxidation and utilization) based on the measurement of e measured 14CO2 and 3H2O production from D-[U-14C]-glucose and D-[5-3H]-glucose, respectively, in isolated 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. The results obtained showed that tthe stimulatory effect of insulin upon 14CO2 and 3H2O production in control islets was not observed in SRD islets. Addition of anti-insulin serum, nifedipine or wortmannin to the medium with 16.7 mM glucose decreased 14CO2 and 3H2O production in control islets but not in SRD islets. Wortmannin did not decrease insulin release induced by 16.7 mM glucose in SRD hamsters, but it did in controls. On account of these results we can conclude that the autocrine stimulatory effect of insulin upon glucose metabolism observed in normal islets is attenuated or even absent in islets from animals with insulin resistance. This decreased islets sensitivity to insulin did not impede the compensatory secretion of insulin to maintain glucose homeostasis, suggesting that, at least in this model, the islets can put forward alternative mechanisms to overcome such defect.