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Albert Salehi

S Albert Salehi

Research team manager

Albert Salehi

Insulin feedback actions: complex effects involving isoforms of islet nitric oxide synthase.

Author

  • Javier Jimenez
  • Ingmar Lundquist
  • Stefanie Obermüller
  • S Albert Salehi

Summary, in English

The present study examined the effects of exogenous insulin on C-peptide release in relation to islet activities of neural constitutive nitric oxide synthase (ncNOS) and inducible NOS (iNOS).



The dose–response curves for glucose-stimulated insulin and C-peptide release from isolated islets were practically identical: 0.05–0.1 nmol/l insulin stimulated, 1–100 nmol/l had no effect, whereas concentrations ≥250 nmol/l (“high insulin”), inhibited C-peptide release. Both the stimulatory and inhibitory effects were abolished by the phosphatidylinositol 3′-kinase inhibitor wortmannin. Addition of a NOS inhibitor partially reversed the inhibitory action of high insulin, but had no effect on the stimulatory action of low insulin (0.1 nmol/l). Moreover, high insulin markedly increased islet ncNOS activity and induced a strong iNOS activity. As shown biochemically and with confocal microscopy, the stimulatory action of high insulin on NOS activities and the associated inhibition of C-peptide release were reversed by raising cyclic AMP through addition of either glucagon-like peptide 1 (GLP-1) or dibutyryl cyclic AMP (Bt2cAMP) to the incubated islets.



We conclude that the positive feedback mechanisms of action of insulin are independent of islet NOS activities and remain unclear. The negative feedback action of insulin, however, can be explained by its ability to stimulate both islet ncNOS activity and the expression and activity of iNOS. The effects on iNOS are most likely transduced through phosphatidylinositol 3′-kinase and are counteracted by raising islet cyclic AMP levels.

Department/s

  • Islet cell physiology
  • Department of Experimental Medical Science

Publishing year

2004

Language

English

Pages

109-118

Publication/Series

Regulatory Peptides

Volume

122

Issue

2

Document type

Journal article

Publisher

Elsevier

Topic

  • Cell and Molecular Biology

Keywords

  • Isoforms of islet nitric oxide synthase
  • Isolated islets
  • Insulin feedback
  • GLP-1
  • Cyclic AMP

Status

Published

Research group

  • Islet cell physiology

ISBN/ISSN/Other

  • ISSN: 1873-1686