Sökning: WFRF:(Ekelund Mats)
> (2005-2009)
> (2007)
> Lundquist Ingmar >
Expression of islet iNOS and inhibition of glucose stimulated insulin release after long-term lipid infusion in the rat is counteracted by PACAP27.
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- Qader, Saleem (författare)
- Lund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Jimenez, Javier (författare)
- Lund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Ekelund, Mats (författare)
- Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Lundquist, Ingmar (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Islet cell physiology,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Lund University Research Groups
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Salehi, Albert (författare)
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(creator_code:org_t)
- American Physiological Society, 2007
- Engelska.
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Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 292:5, s. 1447-1455
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Abstract
Ämnesord
Stäng
- Chronic exposure of pancreatic islets to elevated plasma lipids ( lipotoxicity) can lead to beta-cell dysfunction, with overtime becoming irreversible. We examined, by confocal microscopy and biochemistry, whether the expression of islet inducible nitric oxide synthase ( iNOS) and the concomitant inhibition of glucose-stimulated insulin release seen after lipid infusion in rats was modulated by the islet neuropeptide pituitary adenylate cyclase-activating polypeptide ( PACAP) 27. Lipid infusion for 8 days induced a strong expression of islet iNOS, which was mainly confined to beta-cells and was still evident after incubating islets at 8.3 mmol/l glucose. This was accompanied by a high iNOS-derived NO generation, a decreased insulin release, and increased cyclic GMP accumulation. No iNOS expression was found in control islets. Addition of PACAP27 to incubated islets from lipid-infused rats resulted in loss of iNOS protein expression, increased cyclic AMP, decreased cyclic GMP, and suppression of the activities of neuronal constitutive ( nc) NOS and iNOS and increased glucose-stimulated insulin response. These effects were reversed by the PKA inhibitor H-89. The suppression of islet iNOS expression induced by PACAP27 was not affected by the proteasome inhibitor MG-132, which by itself induced the loss of iNOS protein, making a direct proteasomal involvement less likely. Our results suggest that PACAP27 through its cyclic AMP- and PKA-stimulating capacity strongly suppresses not only ncNOS but, importantly, also the lipid-induced stimulation of iNOS expression, possibly by a nonproteasomal mechanism. Thus PACAP27 restores the impairment of glucose-stimulated insulin release and additionally might induce cytoprotection against deleterious actions of iNOS-derived NO in beta-cells.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Nyckelord
- pituitary adenylate cyclase-activating polypeptide 27
- pancreatic islets
- synthase
- isoforms of nitric oxide
- insulin secretion
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)