Abstract
Compensatory hyperinsulinemia associated with peripheral insulin resistance is a well-recognized metabolic disturbance. However, the mechanism underlying the induction of hyperinsulinemia is unclear. Resistin, a small cysteine-rich protein secreted from adipocytes, is one of the major risk factor of insulin resistance in obesity. The present study employed adenovirus-mediated resistin gene transfer in muscle of the ICR male mice and examined whether acute increases in circulating resistin could cause hyperinsulinemia. In addition, we examined the effect of resistin on pancreatic β-cell function in vitro. Mice expressing resisitin showed increased plasma level of resistin by 2-5 fold, decreased insulin sensitivity and impaired glucose tolerance, accompanied with hyperinsulinemia. In the liver and muscle of resisitin-expressing mice, insulin-induced phosphorylation of Akt was suppressed. Resistin increased 8.3 mM glucose-induced insulin secretion in mice pancreatic islets. Resistin also enhanced glucose-induced cytosolic Ca2+ oscillations in islets, whereas the enhancement was not observed in single β-cells. In addition, resistin inhibited insulin-induced phosphorylation of Akt in islets. These results indicate that over-expression of resistin causes insulin resistance in pancreatic islets, as well as liver and muscle, which may attenuate the autocrine negative-feedback action of insulin on b-cells and thereby enhances insulin secretion. [Jpn J Physiol 55 Suppl:S212 (2005)]
