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DOI: 10.1055/s-2003-38391
Total Parenteral Nutrition-Stimulated Activity of Inducible Nitric Oxide Synthase in Rat Pancreatic Islets is Suppressed by Glucagon-Like Peptide-1
Publikationsverlauf
Received 17 August 2001
Accepted after revision 21 August 2002
Publikationsdatum:
01. April 2003 (online)
Abstract
Long-term total parenteral nutrition (TPN) is associated with elevated plasma lipids and a marked decrease of glucose-stimulated insulin release. Since nitric oxide (NO) has been shown to modulate negatively the insulin response to glucose, we investigated the influence of TPN-treatment on isoforms of islet NO-synthase (NOS) activities in relation to the effect of glucagon-like peptide-1 (GLP-1), a known activator of glucose-stimulated insulin release. Isolated islets from TPN rats incubated at basal glucose (1 mmol/l) showed a modestly increased insulin secretion accompanied by an enhanced accumulation of islet cAMP and cGMP. In contrast, TPN islets incubated at high glucose (16.7 mmol/l) displayed an impaired insulin secretion and a strong suppression of islet cAMP content. Moreover, islet inducible NOS (iNOS) as well as islet cGMP content were greatly increased in these TPN islets. A dose-response study of GLP-1 with glucose-stimulated islets showed that GLP-1 could overcome and completely restore the impaired insulin release in TPN islets, bringing about a marked increase in islet cAMP accumulation concomitant with heavy suppression of both glucose-stimulated increase in islet cGMP content and the activities of constitutive NOS (cNOS) and iNOS. These effects of GLP-1 were mimicked by dibutyryl-cAMP. The present results show that the impaired insulin response of glucose-stimulated insulin release seen after TPN treatment is normalized by GLP-1. This beneficial effect of GLP-1 is most probably exerted by a cAMP-induced suppression of both iNOS and cNOS activities in these TPN islets.
Key words
Pancreatic Islets - Hormones - Isoforms of Nitric Oxide Synthase - Cyclic Nucleotides
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A. Salehi
Department of Physiological Sciences · Division of Pharmacology · University of Lund
BMC F13 · 221 84 Lund · Sweden
Fax: + 46 (46) 222 44 29
eMail: Salehi @farm.lu.se