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Islet beta-cell apoptosis triggered in vivo by interleukin-1beta is not related to the inducible nitric oxide synthase pathway: evidence for mitochondrial function impairment and lipoperoxidation.
- Source :
-
Endocrinology [Endocrinology] 2003 Oct; Vol. 144 (10), pp. 4264-71. Date of Electronic Publication: 2003 Jul 03. - Publication Year :
- 2003
-
Abstract
- IL-1beta is recognized as an effector cytokine contributing to islet beta-cell destruction during diabetes. We have previously shown in vitro that IL-1beta induces nitric oxide (NO) and beta-cell damage. Here, we show that IL-1beta administration in vivo to Wistar rats transiently increases manganese superoxide dismutase activity, whereas inducible NO synthase is not detected, and the levels of nitrate+nitrate do not change. Moreover, a significant decrease of mitochondrial aconitase, leading to a rise of hydroperoxides, and islet beta-cell apoptosis, involving caspase-3 and -8, is observed. Analysis of adhesion molecules in beta-cells showed that intercellular adhesion molecule-1 is highly expressed 48 h after IL-1beta administration and that this is concomitant to the fall of manganese superoxide dismutase activity. Thus, IL-1beta exerts a proapoptotic effect in vivo through mitochondrial enzyme alteration, which is not related to the inducible NO synthase pathway, and dysregulates the immune system through the up-regulation of adhesion molecules.
- Subjects :
- Aconitate Hydratase metabolism
Animals
Caspase 3
Caspase 8
Caspase 9
Caspases metabolism
In Vitro Techniques
Intercellular Adhesion Molecule-1 metabolism
Islets of Langerhans metabolism
Mitochondria enzymology
Nitrates metabolism
Nitric Oxide Synthase Type II
Nitrites metabolism
Rats
Rats, Wistar
Superoxide Dismutase metabolism
Apoptosis physiology
Interleukin-1 pharmacology
Islets of Langerhans drug effects
Islets of Langerhans physiology
Lipid Peroxides metabolism
Mitochondria physiology
Nitric Oxide Synthase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0013-7227
- Volume :
- 144
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 12960105
- Full Text :
- https://doi.org/10.1210/en.2003-0385