The novel imidazoline compound BL11282 potentiates glucose-induced insulin secretion in pancreatic β-cells in the absence of modulation of KATP channel activity

Alexander M. Efanov, Sergei V. Zaitsev, Hans Juergen Mest, Achim Raap, Ioulia B. Appelskog, Olof Larsson, Per Olof Berggren, Suad Efendic

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53 Scopus citations

Abstract

The insulinotropic activity of the novel imidazoline compound BL11282 was investigated. Intravenous administration of BL11282 (0.3 mg · kg-1 · min-1) to anesthetized rats did not change blood glucose and insulin levels under basal conditions, but produced a higher increase in blood insulin levels and a faster glucose removal from the blood after glucose infusion. Similarly, in isolated Wistar rat pancreatic islets, 0.1-100 μmol/l BL11282 potently stimulated glucose-induced insulin secretion but did not modulate basal insulin secretion. Unlike previously described imidazolines, BL11282 did not block ATP-dependent K+ channels. Furthermore, the compound stimulated insulin secretion in islets depolarized with high concentrations of KCl or permeabilized with electric shock. Insulinotropic activity of BL11282 was dependent on activity of protein kinases A and C. In pancreatic islets from spontaneously diabetic GK rats, the imidazoline compound restored the impaired insulin response to glucose. In conclusion, the imidazoline BL11282 constitutes a new class of insulinotropic compounds that exerts an exclusive glucose-dependent insulinotropic activity in pancreatic islets by stimulating insulin exocytosis.

Original languageEnglish (US)
Pages (from-to)797-802
Number of pages6
JournalDiabetes
Volume50
Issue number4
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Efanov, A. M., Zaitsev, S. V., Mest, H. J., Raap, A., Appelskog, I. B., Larsson, O., Berggren, P. O., & Efendic, S. (2001). The novel imidazoline compound BL11282 potentiates glucose-induced insulin secretion in pancreatic β-cells in the absence of modulation of KATP channel activity. Diabetes, 50(4), 797-802. https://doi.org/10.2337/diabetes.50.4.797