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Albert Salehi

S Albert Salehi

Research team manager

Albert Salehi

Glucose stimulates the expression and activities of nitric oxide synthases in incubated rat islets: an effect counteracted by GLP-1 through the cyclic AMP/PKA pathway

Author

  • Javier Jimenez
  • Ingmar Lundquist
  • S Albert Salehi

Summary, in English

We have examined the expression and activity of inducible nitric oxide synthase ( iNOS) and the activity of neuronal constitutive NOS ( ncNOS) in isolated rat pancreatic islets, stimulated by a "hyperglycaemic" concentration of glucose, and whether the NOS activities could be modulated by activation of the cyclic AMP/ protein kinase A ( cyclic AMP/PKA) system in relation to the insulin secretory process. Here, we show that glucose stimulation ( 20 mmol/l) induces iNOS and increases ncNOS activity. No iNOS is detectable at basal glucose levels (3.3 mmol/l). The addition of glucagon-like-peptide 1 (GLP-1) or dibutyryl-cAMP to islets incubated with 20 mmol/l glucose results in a marked suppression of iNOS expression and activity, a reduction in ncNOS activity and increased insulin release. The GLP-1-induced suppression of glucose-stimulated iNOS activity and expression and its stimulation of insulin release is, at least in part, PKA dependent, since the PKA inhibitor H-89 reverses the effects of GLP-1. These observations have been confirmed by confocal microscopy showing the glucose-stimulated expression of iNOS, its suppression by GLP-1 and its reversion by H-89 in beta-cells. We have also found that the NO scavenger cPTIO and the NOS inhibitor L-NAME potentiate the insulin response to glucose, again suggesting that NO is a negative modulator of glucose-stimulated insulin release. We conclude that the induction of iNOS and the increase in ncNOS activity caused by glucose in rat islets is suppressed by the cyclic AMP/ PKA system. The inhibition of iNOS expression by the GLP-1/ cyclic AMP/ PKA pathway might possibly be of therapeutic potential in NO-mediated beta-cell dysfunction and destruction.

Department/s

  • Islet cell physiology

Publishing year

2005

Language

English

Pages

221-230

Publication/Series

Cell and Tissue Research

Volume

319

Issue

2

Document type

Journal article

Publisher

Springer

Topic

  • Cell Biology

Keywords

  • iNOS
  • cNOS
  • glucose toxicity
  • (male Sprague Dawley)
  • rat
  • pancreatic islets
  • insulin secretion

Status

Published

Research group

  • Islet cell physiology

ISBN/ISSN/Other

  • ISSN: 1432-0878