Inhibition of glucose-stimulated insulin release by α2-adrenoceptor activation is parallelled by both a repolarization and a reduction in cytoplasmic free Ca2+ concentration

T. Nilsson, P. Arkhammar, P. Rorsman, P. O. Berggren

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Effects of the α2-adrenergic agonist clonidine on insulin release, membrane potential, and cytoplasmic free Ca2+ concentration ([Ca2+](i)) were investigated using pancreatic β-cells isolated from obese hyperglycemic mice. Addition of 2 μM clonidine promptly inhibited glucose-stimulated insulin release, an effect accompanied by a lowering in both membrane potential and [Ca2+](i). Within minutes, the effect on Ca2+ was partly reversed, [Ca2+](i) attaining a new level, although still significantly lower than in the absence of agonist. This late increase in [Ca2+](i) was inhibited by 50 μM D-600, a blocker of voltage-activated Ca2+ channels. The inhibitory effects of clonidine on membrane potential, [Ca2+](i), and insulin release were abolished by 5 μM of the α2-adrenergic antagonist yohimbine. Depolarization with high K+ increased [Ca2+](i) also in the presence of clonidine, conditions accompanied by only a minute release of insulin. Secretion was, however, partly restored by subsequent addition of 20 mM glucose. Addition of 5 mM Ca2+ transiently reversed the effects of clonidine on both membrane potential and [Ca2+](i). Although the clonidine-induced repolarization should be enough for closing the voltage-activated Ca2+ channels with a resulting decrease in [Ca2+](i), a direct interaction of the agonist with these channels cannot be excluded. The fact that it was possible to increase [Ca2+](i) with only a minor effect on insulin release suggests that the inhibitory effect of clonidine not only is due to a reduction in [Ca2+](i), but also involves interference with some more distal step in the insulin secretory machinery.

Original languageEnglish (US)
Pages (from-to)1855-1860
Number of pages6
JournalJournal of Biological Chemistry
Volume263
Issue number4
StatePublished - Jan 1 1988

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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