Impaired insulin secretion in human diabetes mellitus. Interactions between naloxone, phentolamine and lysine acetylsalicylate upon glucose induced insulin release

D. Giugliano, P. Di Pinto, A. Ceriello, F. Saccomanno, N. Passariello, F. D'Onofrio

Research output: Contribution to journalArticle

Abstract

Non insulin-dependent diabetes mellitus (Type II) is characterized by the loss of the acute insulin response to glucose. Met-enkephalin, catecholamines and prostaglandin E (PGE) have all been reported to inhibit the acute insulin response to glucose in normal humans. To evaluate the hypothesis that an increased sensitivity to these endogenous substances may play a role in defective insulin secretion in diabetes, we evaluated the effects of three blocking drugs upon the impaired insulin response to glucose in Type II diabetic subjects, as well as glucose-induced insulin secretion in normal humans. In diabetics, acute insulin responses to glucose were significantly increased by all the agents tested (naloxone, phentolamine and lysine acetylsalicylate), but only the cycloxygenase inhibitor significantly augmented second phase insulin secretion and glucose disappearance rates. The combined infusion of the three agents caused a striking increase of the acute insulin response to glucose (response before : 3 ± 2 uU/ml; after : 22 ± 6 uU/ml, p <0.01). This was accompanied by a ninefold augmentation of the second phase of insulin secretion which was the result of a synergistic interaction between the three drugs (response significantly higher than the sum of single effects). In normals, insulin responses to glucose were also significantly increased by the combined infusions of the drugs, but to a significantly lesser extent than that of diabetics. This different degree of insulin potentiation betwee normals and diabetics under the infusion of the three agents persisted even when the prestimulus glucose levels of normals was matched to that of diabetics by a glucose infusion. These results indicate that (1) in Type II diabetics, the combined infusion of the three blocking agents produces significant increases in both first (additive interaction) and second (synergistic interaction) phase insulin secretion, and (2) in normals, there is neither additive nor synergistic interaction between these drugs in augmenting insulin responses to glucose. These data are compatible with an increased sensitivity of the diabetic beta-cell to the effects of these three drugs and also suggest a role for endogenous substances (met-enkephalin, catecholamines and PGE) in the pathogenesis of defective insulin secretion of human Type II diabetes.

Original languageEnglish
Pages (from-to)350-358
Number of pages9
JournalDiabete et Metabolisme
Volume11
Issue number6
Publication statusPublished - 1985

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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