The possibility that insulin-induced feedback inhibition was responsible for the phasic release of insulin during continuous stimulation was investigated in the in vitro perfused rat pancreas. Continuous perfusion with selected concentrations of glucose (110 mg./100 ml.) ortolbutamide (300 μg./ml.) produced the characteristic initial rise and fall of insulin secretion; there was no rebound to high secretion rates during the later periods of stimulation with either agent. Rat insulin, perfused in a variety of patterns to simulate both early and steady state levels of endogenous insulin secretion, neither obliterated nor significantly affected the initial spike of endogenous insulin release elicited by either glucose or tolbutamide. There was no evidence of dampened oscillation or delayed inhibition by exogenous insulin. Results indicate insulin-induced feedback inhibition is not responsible for phasic insulin secretion; the previoussuggestions that this phenomenon reflects a substrate-induced feedback inhibition or a threshold-sensitive packet storage system are viable possibilities.

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