THE USE OF INSULIN IN THE PRODUCTION OF L-LEUCINE-INDUCED HYPOGLYCEMIA IN NORMAL DOGS*

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Abstract
L-leucine induces hypoglycemia in a few patients with idiopathic hypoglycemia of infancy or insulin secreting pancreatic tumors. Because this "sensitivity" to L-leucine has been associated with hyperinsulinism and/or hypoglycemia we attempted to experimentally induce leucine hypoglycemia in normal dogs by prior or concomitant administration of insulin. As was true in normal people L-leucine had little or no blood glucose lowering effect when given alone. However, a significant hypoglycemic effect could be obtained with L-leucine if ultralente insulin was given 14 hours previously. L-leucine given with rapid or sustained infusions of regular insulin slowed the recovery from hypoglycemia. The demonstration that small arterio-venous blood glucose differences were associated with this prolonged recovery from hypoglycemia suggests that L-leucine acts by inhibiting the hyperglycemic response to hypoglycemia. Finally, the production of "leucine-induced hypoglycemia" in normal dogs suggests that the effect of L-leucine is not limited to a few patients with specific diseases, but represents a generalized response in situations characterized by hyperinsulinism or hypoglycemia, or both.