Effect of an enkephalin-analogue (FK 33-824) on glucose tolerance in man

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Abstract
The effect of a methionine-enkephalin analog (FK 33-824) on glucose tolerance was studied in man. Groups of 5 to 8 normal subjects were given a 0.5 mg i.m. injection of the drug or placebo just before a 100 g oral glucose load or a 0.5 g/kg i.v. glucose load. In the enkephalin analog treated subjects, diminished insulin response to glucose was observed following the oral glucose load, with insulin values significantly lower than in the controls from time 10 to 90 min, but no corresponding change in the glucose curve. This effect was not observed when glucose was given i.v. in another group of 5 subjects in whom the significant blunting of the insulin response was accompanied by a significant decrease in glucose tolerance. In man, enkephalin produces a decrease in insulin secretion in response to both oral and i.v. glucose loads [and may play a role in non-insulin-dependent diabetes]. The absence of any marked impairment in glucose tolerance in the oral test in spite of the decreased insulin response suggests that enkephalin might have an additional effect in delaying glucose absorption.