Chronic suppression of insulin by diazoxide alters the activities of key enzymes regulating hepatic gluconeogenesis in Zucker rats.

Objectives: Chronic attenuation of hyperinsulinemia by diazoxide (DZ), an inhibitor of glucose-mediated insulin secretion, improved insulin sensitivity and glucose tolerance and caused down-regulation of lipid metabolizing enzymes in adipose tissue and decreased the rate of weight gain in mildly hyperglycemic obese Zucker rats. Since the liver plays a central role in glucose homeostasis, we studied the effect of chronic insulin suppression on key insulin-sensitive enzymes regulating hepatic gluconeogenesis.

Methods: DZ (150 mg/kg per day) or vehicle (control) was administered to 7-week-old female obese and lean Zucker rats for a period of 4 weeks.