The acute release of insulin in response to graded pulse doses of intravenous glucose was assessed in twelve healthy subjects before and during treatment with tolbutamide, ethanol and tolbutamide plus ethanol. A linear relationship was observed between the mean 3′-5′ insulin increment (ΔIRI) and the glucose dose up to five gm.; thereafter, the response plateaued. Insulin increments over baseline prior to treatment ranged from 12 ± 1.8 μU./ml. for 1.0 gm. to 124 ± 11.3 μU./ml. (mean ± S.E.M.) for 20.0 gm. Pretreatment with tolbutamide, ethanol and tolbutamide plus ethanol resulted in protentiation of the acute phase insulin release and enhanced glucose disappearance with glucose doses of 10 gm. and less. With the 20 gm. glucose dose, no significant potentiation of insulin release nor enhancement of glucose disappearance could be demonstrated. Potentiation of insulin release by tolbutamide pretreatment also required administration of the drug on the day of the test. We suggest that studies involving the effects of agents on the dynamics of acute phase insulin response to glucose be done with glucose doses which produce submaximal β-cell stimulation.

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