Evidence for a role of exogenous or endogenous hyperlactatemia in insulin secretion in the dog

Various types of experimental hyperlactatemia were induced in the normal anesthetized dog, and the changes in insulin secretion were measured in the pancreatico-duodenal vein. Hyperlactatemia was induced in the absence or in the presence of an infusion of sodium dichloroacetate (DCA), which activates pyruvate dehydrogenase. 1. Exogenous hyperlactatemia: The infusion of sodium L(+)lactate resulted in a strong increase in blood lactate level which was accompanied by a significant increase in the insulin output from the pancreatico-duodenal vein. The administration of DCA did not counteract the increase in lactate level and did not modify insulin output either. 2. Endogenous hyperlactatemia: This was induced either by pharmacological means: the subcutaneous injection of an antidiabetic biguanide, phenformin (20 mg/kg), or by physiological means: intense muscular work. In both cases an increase in the lactate level and in insulin output was recorded. The administration of DCA suppressed the hyperlactatemia and counteracted the increase in insulin output. These results show that there is a relationship between lactate level and insulin secretion, and give evidence for a role of endogenous lactate in the regulation of insulin secretion.