Sustained hyperglycemia and insulin resistance induced by dietary restriction

This investigation considered whether defects in insulin secretion and insulin action may result in the development of sustained hyperglycemia induced by refeeding standard chow pellets. Hyperglycemia, sustained for 36 h was induced, in mice that ate standard chow pellets ad libitum after 48 h fasting, but not 24 h fasting. In 48 h-fasted mice, serum insulin levels were remarkably low and the ability of insulin secretion to respond to glucose was decreased, although insulin-stimulated glucose disposal was not impaired. However, hyperinsulinemia was observed after refeeding for 12 h. The 12 h-refed mice had impaired glucose tolerance and were remarkably insulin resistant. These results suggest that hyperglycemia induced by the fasting-refeeding was caused by hyperphagia and the failure of insulin secretion, and maintained the resulting induced insulin resistance.