The Insulin Secretagogues Glibenclamide and Repaglinide Do Not Influence Growth Hormone Secretion in Humans but Stimulate Glucagon Secretion during Profound Insulin Deficiency

Torben Østergård, Kristine B. Degn, Mari Anne Gall, Richard D. Carr, Johannes D. Veldhuis, Mads K. Thomsen, Robert A. Rizza, Ole Schmitz

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

In vitro data have recently suggested that sulfonylureas (SUs) enhance GH secretion by modulating the effects of GHRH and somatostatin in pituitary cells. The present study was undertaken to explore in more detail a possible influence of a single dose of SU (glibenclamide) and a non-SU (repaglinide) insulin secretagogue on circulating GH dynamics. Ten C-peptide-negative type 1 diabetic individuals were examined on three occasions in random order. Either glibenclamide (10.5 mg), repaglinide (8 mg), or placebo was administered after overnight normalization of plasma glucose by iv insulin infusion. Subsequently, GH concentrations were measured regularly after stimulation with GHRH (bolus 0. 1 μg/kg) alone and during concomitant infusion with somatostatin (7 ng·kg-1·min-1). Insulin was replaced at baseline levels (0.25 mU·kg-1·min-1) and plasma glucose clamped at 5-6 mmol/liter. Overall, there were no significant statistical differences in GH responses determined as either GH peak concentrations, integrated levels of GH, or secretory burst mass of GH during the experimental protocol. In contrast, plasma glucagon concentrations were significantly increased during glibenclamide and repaglinide exposure. The present experimental design does not support the hypothesis that acute administration of pharmacological doses of the oral antihyperglycemic agents glibenclamide and repaglinideper se enhance GH release in humans. Additionally, this study shows that these potassium channel inhibitors seem to stimulate glucagon secretion in people who have severe intraislet insulin deficiency (e.g. type 1 diabetes). However, extrapolation of our findings to type 2 diabetic individuals should be done with some caution.

Original languageEnglish (US)
Pages (from-to)297-302
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number1
DOIs
StatePublished - Jan 1 2004

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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