A Comparison of Leucine- and Acetoacetate-induced Hypoglycemia in Man*

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Abstract
Equimolar amounts of leucine and acetoacetate were injected intravenously into 10 healthy subjects before and after administration of chlorpropamide. Before the administration the leucine and the acetoacetate induced similar mild hypoglycemia. After the administration of the chlorpropamide, acetoacetate produced the same mild hypoglycemia, but leucine now produced intense hypoglycemia. Insulin did not rise in the peripheral plasma after the administration of the acetoacetate. Increases in plasma levels of acetoacetate after infusions of leucine were small and followed decrease in blood levels of glucose. In two subjects who received infusions of isovalerate after pretreatment with chlorpropamide there were no decreases in blood glucose. The increases in plasma acetoacetate were greater and more rapid than after the administration of leucine. Plasma levels of acetoacetate rose sharply after the administration of acetoacetate. These findings suggest that acetoacetate lowers blood glucose, that leucine itself rather than acetoacetate derived from its catabolism causes insulin release and hypoglycemia after its administration and that if acetoacetate induces insulin release in man, the mechanism must be different from that activated by leucine.