Endothelin-1 decreases glucose, inhibits glucagon, and stimulates insulin release in the rat

Abstract

The effects of endothelin-1 (ET-1) infusion at 0, 25, 50, and 75 ng/kg/min on blood glucose, insulin, and ET-1 levels were determined in anesthetized rats. In a separate group of rats, ET-1 was infused at 75 ng/kg/min and glucagon and glucose levels were determined. In another group of rats, the effect on blood glucose of glucagon infusion at 0.2 ng/kg/min with ET-1 infusion at 75 ng/kg/min for 30 minutes was determined. Glucose decreased 10 minutes after initiation of ET-1 infusion at 75 ng/kg/min and at 15 minutes during ET-1 infusion at 25 and 50 ng/kg/min. After 45 minutes, glucose decreased by 1.05 ± 0.1, 1.44 ± 0.11, and 1.39 ± 0.22 mmol/L and ET-1 increased by 4.4 ± 0.8, 5.2 ± 1.2, and 11.2 ± 0.8 pmol/L during ET-1 infusion at 25, 50, and 75 ng/kg/min, respectively. Insulin levels increased during ET-1 infusion of 50 ng/kg/min at 30 and 45 minutes by 300 ± 75 and 405 ± 120 pmol/L, respectively. During ET-1 infusion of 75 ng/kg/min, insulin increased at 45 minutes by 570 ± 180 pmol/L. Glucagon decreased during ET-1 infusion at 15 minutes associated with a decrease in glucose. Glucagon levels subsequently returned to baseline values despite a continued decline in glucose levels. Glucagon infusion at 0.2 μg/kg/min prevented the early ET-1-induced hypoglycemia. These findings demonstrate that ET-1 decreased blood glucose initially associated with a decrease in glucagon and subsequently associated with enhanced insulin release.