Nitric Oxide Synthase in Pancreatic Islets During Trauma and Parenteral Feeding

Research output: ThesisDoctoral Thesis (compilation)

Abstract

The influence of trauma (acute pancreatitis) or total parenteral nutrition (TPN) on pancreatic islet hormone secretion in relation to islet expression of inducible nitric oxide synthase (iNOS) was investigated. Acute pancreatitis resulted in an impaired glucose-stimulated insulin secretion (GSIS) which was found to be parallelled by a marked expression of iNOS and an exaggerated NO production in the pancreatic islets. A characteristic feature of long term TPN-treatment is hyperlipidemia and euglycaemia, since the major component of TPN solution is intralipid (IL). TPN treatment impairs GSIS at least in part through a reduced cyclic AMP production in parallel with an exclusive expression of iNOS, which was reflected in an increased NO production accompanied by enhanced cyclic GMP formation by islets. Agents stimulating cyclic AMP/Protein kinase A (PKA) i.e. PACAP27 and PACAP38 were capable of not only inhibiting neuronal constitutive NOS (ncNOS) but also counteracting the expression of iNOS induced by intralipid infusion. The suppressed NO production in the presence of PACAPs was reflected in a suppressed cyclic GMP and a marked increase in cyclic AMP production by pancreatic islets. A short-term study revealed that a "hyperglycaemic or hyperlipidemic period" as short as 24 hours stimulated the expression and activity of iNOS in the islets. Finally the effect of ghrelin (gastric hormone) on islet hormone secretion and NOS isoenzymes activities was also studied. The inhibitory action of ghrelin on GSIS and the stimulatory effect on the glucagon secretion was accompanied by an increased ncNOS activity. However, such effects of ghrelin were only observed at slightly higher and supra-physiological concentrations (in vitro study). Furthermore, TPN-animals displayed extreme low plasma and tissue levels of ghrelin. Thus, ghrelin does not seem to have any significant role in the reduced GSIS and iNOS expression seen during TPN-treatment.

Taken together the data suggest that, besides trauma, hyperglycaemia and hyprelipidemia are able to induce pathophysiological changes in pancreatic islets (iNOS expressing and reduced GSIS) implicating that the nutritional state should be regarded as an important factor for the normal function of islets.

Details

Authors
  • Saleem Qader
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Other Clinical Medicine

Keywords

  • Surgery, orthopaedics, traumatology, Kirurgi, ortopedi, traumatologi, Gastroenterologi, Gastro-enterology, Pancreatitis, Ghrelin, TPN, cNOS, iNOS, PACAP, VIP, cAMP, Pancreatic islets, Insulin secretion
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date2004 Sep 23
Publisher
  • Saleem Sa'aed Qader, MD, MSc, MPH, Department of Surgery, Lund University Hospital, SE-221 85 Lund, Sweden,
Print ISBNs91-628-6216-2
Publication statusPublished - 2004
Publication categoryResearch

Bibliographic note

Defence details Date: 2004-09-23 Time: 10:15 Place: Lecture Room 3, Main Building, Lund University Hospital External reviewer(s) Name: Hammarqvist, Folke Title: Docent Affiliation: Huddinge, Sweden --- Article: I. Saleem S. Qader, Mats Ekelund, Roland Andersson, Stefanie Obermuller and Albert Salehi. Acute pancreatitis, expression of inducible nitric oxide synthase and defective insulin secretion. Cell Tissue Res (2003) 313:271–279.II. Albert Salehi, Saleem S. Qader, Eva Ekblad and Mats Ekelund. Defective insulin secretion during total parenteral nutrition in rat and its normalization by pituitary adenylate cyclase-activating polypeptide 27. Regul Pept. (2004)119: 83-91.III. Saleem S. Qader, Javier Jimenez-Feltström, Mats Ekelund, Ingmar Lundquist and Albert Salehi. Expression of islet inducible nitric oxide synthase and inhibition of glucose stimulated insulin release after long-term lipid infusion in the rat is counteracted by PACAP27: Submitted to AJP-Cell Physiology.IV. Mats Ekelund, Saleem S. Qader, Javier Jimenez-Feldström and Albert Salehi. Selective induction of inducible nitric oxide synthase in pancreatic islet of rat after an intravenous glucose challenge: Manuscript.V. Saleem S. Qader, Albert Salehi, Rolf Håkanson, Ingmar Lundquist and Mats Ekelund. Long-term infusion of nutrients (total parenteral nutrition) suppresses circulating ghrelin in food-deprived rat: Submitted to Regulatory Peptides.VI. Saleem S. Qader, Ingmar Lundquist, Mats Ekelund, Rolf Håkanson and Albert Salehi. Ghrelin activates neuronal constitutive nitric oxide synthase in pancreatic islet cells while inhibiting insulin release and stimulating glucagon release: Submitted to Regulatory Peptides.

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