INTERACTION BETWEEN EPINEPHRINE, PROSTAGLANDIN-E, AND MET-ENKEPHALIN IN THE REGULATION OF INSULIN RELEASE IN MAN

  • 1 January 1985
    • journal article
    • research article
    • Vol. 11  (5) , 295-302
Abstract
Prostaglandin E (PGE), epinephrine and met-enkephalin and three endogenous substances normally present in the endocrine pancreas which have been reported to inhibit glucose-induced insulin secretion in normal humans. To evaluate possible synergistic interactions between these inhibitory agents upon the regulation of insulin release in man, we examined the effects of PGE, epinephrine and the long-acting met-enkephalin analogue FK 33-824, given alone or in combination, upon glucose-induced insulin secretion in normal man. The infusion of the three agents at doses known to affect insulin secretion (10 .mu.g/min, 15 ng/kg/min, 0.5 mg im, respectively) produced the expected inhibitory effects upon insulin responses to an intravenous glucose challenge. The infusion of the three agents at doses which does not produce per se any significant change of insulin responses to glucose (5 .mu.g/min, 5 ng/kg/min, 0.2 mg i.m., respectively), caused a significant inhibition of this response when given in combination. In particular, the acute insulin response to glucose decreased from a control value of 50 .+-. 9 .mu.U/ml to a value of 21 .+-. 6 .mu.U/ml (p < 0.02). The inhibitory effect of epinephrine (15 ng/kg/min) upon glucose-induced insulin secretion was partially reversed by sodium salicylate, an inhibitor of endogenous prostaglandin synthesis, which increased but not normalized, either the acute insulin response and the glucose disappearance rates. Similarly, the negative effect of FK 33-824 upon glucose-induced insulin secretion was reversed by sodium salicylate. Similar findings were also obtained with indomethacin, another structurally unrelated inhibitor of endogenous prostaglandin synthesis. These results in normal man seem to indicate that (1) a synergistic interaction may be operative between PGE, epinephrine and met-enkephalin to inhibit glucose-induced insulin release; (2) endogenous prostaglandins may play a role in the mediation of epinephrine and met-enkephalin effect in the beta-cell.

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