Insulin signaling proteins in pancreatic islets of insulin-resistant rats induced by glucocorticoid

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chronic administration of glucocorticoids induces insulin resistance that is compensated by an increase in beta-cell function and mass. Since insulin signaling is involved in the control of beta-cell function and mass, we investigated the content of insulin pathway proteins in pancreatic islets. Rats were made insulin resistant by daily administration of dexamethasone (1 mg/kg, b.w., i.p.) for 5 consecutive days (DEX), whilst control rats received saline (CTL). Circulating insulin and insulin released from isolated islets were measured by radioimmunoassay whereas the content of proteins was analyzed by Western blotting. DEX rats were hyperinsulinemic and exhibited augmented insulin secretion in response to glucose (P < 0.01). The IR alpha-subunit, IRS-1, Shc, AKT, p-p70(S6K), ERK1/2, p-ERK1/2, and glucocorticoid receptor protein levels were similar between DEX and CTL islets. However, the IR beta-subunit, p-IR beta-subunit, IRS-2, PI3-K, p-AKT and p70(S6K) protein contents were increased in DEX islets (P < 0.05). We conclude that IRS-2 may have a major role, among the immediate substrates of the insulin receptor, to link activated receptors to downstream signaling components related to islet function and growth in this insulin-resistant rat model.