Insulin signaling proteins in pancreatic islets of insulin-resistant rats induced by glucocorticoid.
Chronic administration of glucocorticoids induces insulin resistance that is compensated by an increase in p-cell function and mass. Since insulin signaling is involved in the control of p-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 (1mg/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 IRa-subunit, IRS-1, Shc, AKT, p-p70S6K, ERK1/2, p-ERK1/2, and glucocorticoid receptor protein levels were similar between DEX and CTL islets. However, the IRp-subunit, p-IRp-subunit, IRS-2, PI3-K, p-AKT and p70S6K 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.
Department of Anatomy, Cell Biology and Physiology and Biophysics, Institute of Biology, Universidade Estadual de Campinas - UNICAMP, Campinas, SP, Brazil.
Flávia M M
FM
De Paula
Antonio C
AC
Boschero
Everardo M
EM
Carneiro
José R
JR
Bosqueiro
Alex
A
Rafacho
D000818:Animals; D003907:Dexamethasone / Q000009:adverse effects*; D005938:Glucocorticoids / Q000009:adverse effects*; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism; D015398:Signal Transduction
D005938:Glucocorticoids; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D055765:Shc Signaling Adaptor Proteins; D003907:Dexamethasone