Effect of diazoxide on golden hamsters with chronic hypoglycemia due to a transplantable islet-cell tumor.

Abstract

The development of the transplantable islet-cell tumor in the golden hamster induces, within six to eight weeks, a severe fasting hypoglycemia and a significant increase in the circulating levels of plasma insulin. The chronic oral administration of diazoxide (250 mg/kg/day) induces a significant increase in blood sugar in fed animals. The elevation of blood sugar is not significant in overnight-fasted animals. The diazoxide-induced hyperglycemia is not accompanied by any reduction in plasma insulin level. The acute intraperitoneal infection of diazoxide (100 mg/kg) markedly increases blood glucose in normal overnight-fasted hamsters; concomitantly, circulating plasma insulin levels are significantly reduced. In the overnight-fasted tumor-bearing animals, the acute injection of diazoxide induces a rise in blood sugar usually accompanied by a paradoxical rise in plasma immunoreactive insulin. Neither depletion of the catecholamine stores by previous administration of reserpine nor β-receptor blockade by propranolol administration can suppress the hyperglycemic response to the acute injection of diazoxide. These data clearly indicate that, in hamster bearing the transplantable islet-cell tumor, the hyperglycemic action of diazoxide does not result from an inhibition of insulin secretion and strongly suggest that this effect is independent of catecholamine release. This conclusion is supported by the lack of effect of diazoxide on both tumor and adrenal catecholamine content.