S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats

►Insulin receptor antagonist S961 causes hyperglycemia, hyperinsulinemia and insulin resistance in rats. ►Peroxysome-proliferator-activated-receptor-gamma agonist pioglitazone improves S961 induced hyperglycemia and glucose intolerance. ►Long term treatment with insulin receptor antagonist S961 results in the decreased adiposity and hepatic glycogen content. ►Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms.