Imidazoline compounds stimulate insulin release by inhibition of K(ATP) channels and interaction with the exocytotic machinery

Sergei V. Zaitsev, Alexandre M. Efanov, Ioulia B. Efanova, Olof Larsson, Claes Göran Östenson, Gerald Gold, Per Olof Berggren, Suad Efendić

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

A novel imidazoline compound, RX671024, was used to investigate the mechanisms by which imidazoline derivatives promote insulin secretion in rat pancreatic β-cells and HIT T15 cells. RX871024 stimulated insulin release from rat pancreatic β-cells and HIT T15 cells in a glucose-dependent way. This effect was not related to α2-adrenergic, I1-, and I2-imidazoline receptors. RX871024 promoted insulin release by at least two modes of action. One included an increase in cytoplasmic free Ca2+ concentration ([Ca2+](i)), subsequent to blocking of ATP-dependent K+ channels, membrane depolarization, and activation of voltage-dependent Ca2+ channels. The other, a more distal effect of imidazoline, affected the exocytotic machinery and was unrelated to changes in membrane potential and [Ca2+](i). The mechanism of RX871024-induced insulin release was dependent on protein kinases A and C. The sensitizing effect of a low dose of RX871024 on glucose- induced insulin secretion suggests that imidazoline compounds of this kind may constitute the basis for development of a new class of oral hypoglycemic agents.

Original languageEnglish (US)
Pages (from-to)1610-1618
Number of pages9
JournalDiabetes
Volume45
Issue number11
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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