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Albert Salehi

S Albert Salehi

Research team manager

Albert Salehi

Imidazoline-induced amplification of glucose- and carbachol-stimulated insulin release includes a marked suppression of islet NO generation in the mouse.

Author

  • Sandra Meidute
  • Henrik Mosén
  • Ingmar Lundquist
  • S Albert Salehi

Summary, in English

Aim: The role of islet nitric oxide (NO) production in insulin releasing mechanisms is unclear. We examined whether the beneficial effects of the imidazoline derivative RX 871024 (RX) on beta-cell function might be related to perturbations of islet NO production. Methods: Experiments were performed with isolated islets or intact mice challenged with glucose or carbachol with or without RX treatment. Insulin was determined with radioimmunoassay, NO generation with high-performance liquid chromatography and expression of inducible NO-synthase (iNOS) with confocal microscopy. Results: RX treatment, in doses lacking effects on basal insulin, greatly amplified insulin release stimulated by the NO-generating secretagogues glucose and carbachol both in vitro and in vivo. RX also improved the glucose tolerance curve. Islets incubated at high glucose (20 mmol/l) displayed increased NO production derived from both neuronal constitutive NO-synthase (ncNOS) and iNOS. RX abrogated this glucose-induced NO production concomitant with amplification of insulin release. Confocal microscopy revealed abundant iNOS expression in beta-cells after incubation of islets at high but not low glucose. This was abolished after RX treatment. Similarly, islets cultured for 24 h at high glucose showed intense iNOS expression in beta-cells. This was abrogated with RX and followed by an amplified glucose-induced insulin release. Conclusion: RX effectively counteracts the negative impact of beta-cell NO generation on insulin release stimulated by glucose and carbachol suggesting imidazoline compounds by virtue of NOS-inhibitory properties being of potential therapeutic value for treatment of beta-cell dysfunction in hyperglycaemia and type 2 diabetes.

Department/s

  • Islet cell physiology
  • Clinical Physiology (Lund)

Publishing year

2009

Language

English

Pages

375-383

Publication/Series

Acta Physiologica

Volume

195

Issue

3

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Physiology

Keywords

  • islet nitric oxide synthase isoenzymes
  • insulin release
  • imidazoline RX 871024
  • cholinergic stimulation
  • glucose stimulation

Status

Published

Research group

  • Islet cell physiology

ISBN/ISSN/Other

  • ISSN: 1748-1708