Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Role of Inducible Nitric Oxide Synthase and Melatonin in Regulation of β-cell Sensitivity to Cytokines
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The mechanisms of β-cell destruction leading to type 1 diabetes are complex and not yet fully understood, but infiltration of the islets of Langerhans by autoreactive immune cells is believed to be important. Activated macrophages and T-cells may then secrete cytokines and free radicals, which could selectively damage the β-cells. Among the cytokines, IL-1β, IFN-γ and TNF-α can induce expression of inducible nitric synthase (iNOS) and cyclooxygenase-2. Subsequent nitric oxide (NO) and prostaglandin E2 (PGE2) formation may impair islet function.

In the present study, the ability of melatonin (an antioxidative and immunoregulatory hormone) to protect against β-cell damage induced by streptozotocin (STZ; a diabetogenic and free radical generating substance) or IL-1β exposure was examined. In vitro, melatonin counteracted STZ- but not IL-1β-induced islet suppression, indicating that the protective effect of melatonin is related to interference with free radical generation and DNA damage, rather than NO synthesis. In vivo, non-immune mediated diabetes induced by a single dose of STZ was prevented by melatonin.

Furthermore, the effects of proinflammatory cytokines were examined in islets obtained from mice with a targeted deletion of the iNOS gene (iNOS -/- mice) and wild-type controls. The in vitro data obtained show that exposure to IL-1β or (IL-1β + IFN-γ) induce disturbances in the insulin secretory pathway, which were independent of NO or PGE2 production and cell death. Initially after addition, in particular IL-1β seems to be stimulatory for the insulin secretory machinery of iNOS –/- islets, whereas IL-1β acts inhibitory after a prolonged period. Separate experiments suggest that the stimulatory effect of IL-1β involves an increased gene expression of phospholipase D1a/b. In addition, the formation of new insulin molecules appears to be affected, since IL-1β and (IL-1β + IFN-γ) suppressed mRNA expression of both insulin convertase enzymes and insulin itself.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2003. , p. 58
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1280
Keywords [en]
Cell biology, β-cell, Cyclooxygenase, Cytokine, Diabetes, IFN-γ, IL-1β, iNOS, Insulin, Melatonin, Nitric oxide, Pancreatic islets, Phospholipase D, Prostaglandin E2, Streptozotocin
Keywords [sv]
Cellbiologi
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-3537ISBN: 91-554-5704-5 (print)OAI: oai:DiVA.org:uu-3537DiVA, id: diva2:163168
Public defence
2003-09-27, B22, Biomedical Centre (BMC), Uppsala, 10:15
Opponent
Supervisors
Available from: 2003-09-03 Created: 2003-09-03 Last updated: 2018-01-13Bibliographically approved
List of papers
1. Melatonin protects against streptozotocin, but not Interleukin-1β-induced damage of rodent pancreatic β-cells
Open this publication in new window or tab >>Melatonin protects against streptozotocin, but not Interleukin-1β-induced damage of rodent pancreatic β-cells
2001 In: J. Pineal Res., ISSN 0742-3098, Vol. 30, no 3, p. 157-165Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90711 (URN)
Available from: 2003-09-03 Created: 2003-09-03Bibliographically approved
2. Cytokine-induced inhibition of insulin release from mouse pancreatic β-cells deficient in inducible nitric oxide synthase
Open this publication in new window or tab >>Cytokine-induced inhibition of insulin release from mouse pancreatic β-cells deficient in inducible nitric oxide synthase
2001 In: Biochem. Biophys. Res. Commun., ISSN 0006-291, Vol. 281, no 2, p. 396-403Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90712 (URN)
Available from: 2003-09-03 Created: 2003-09-03Bibliographically approved
3. Cytokine-induced prostaglandin E2 formation is reduced from mouse pancreatic islets deficient in inducible nitric oxide synthase
Open this publication in new window or tab >>Cytokine-induced prostaglandin E2 formation is reduced from mouse pancreatic islets deficient in inducible nitric oxide synthase
(English)Manuscript (Other academic)
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-90713 (URN)
Available from: 2003-09-03 Created: 2003-09-03 Last updated: 2018-01-13
4. Role of phospholipase D, insulin and proinsulin convertase gene expression in altered insulin secretion from β-cells deficient in inducible nitric oxide synthase following IL-1β and IFN-γ exposure
Open this publication in new window or tab >>Role of phospholipase D, insulin and proinsulin convertase gene expression in altered insulin secretion from β-cells deficient in inducible nitric oxide synthase following IL-1β and IFN-γ exposure
Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-90714 (URN)
Available from: 2003-09-03 Created: 2003-09-03 Last updated: 2010-01-13Bibliographically approved

Open Access in DiVA

fulltext(677 kB)2171 downloads
File information
File name FULLTEXT01.pdfFile size 677 kBChecksum MD5
92e14b485020cc653942af1d5fa46720f875ebb3e081e55de2d0c7d06b7318fa2bcc0308
Type fulltextMimetype application/pdf
Buy this publication >>

By organisation
Department of Medical Cell Biology
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 2171 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 1310 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf