Kinetics of the early insulin response of the perfused rat pancreas to various metabolites and tolbutamide.

The collection every 15 seconds of the portal effluent of the isolated and perfused rat pancreas permitted the following observations: while the insulin response to tolbutamide (250 or 125 mug/ml) occurred immediately, that to glucose (15 mM), or to 1-leucine (15 mM) was delayed by 60-90 seconds. The response to d-glyceraldehyde occurred slightly but significantly more quickly than that of glucose. The response to alpha-keto-isocaproate was an intense and immediate one. Isovalerate elicited no insulin discharge. These results suggest that d-glucose and l-leucine have to be metabolized to stimulate insulin secretion and that alpha-keto-isocaproate seems to be a direct and specific signal.