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Increasing uncoupling protein-2 in pancreatic beta cells does not alter glucose-induced insulin secretion but decreases production of reactive oxygen species

Davis-Lameloise, N.
Perreten, H.
Becard, D.
Gjinovci, A.
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Published in Diabetologia. 2007, vol. 50, no. 1, p. 84-93
Collection Open Access - Licence nationale Springer
Abstract AIMS/HYPOTHESIS: Levels of uncoupling protein-2 (UCP2) are regulated in the pancreatic beta cells and an increase in the protein level has been associated with mitochondrial uncoupling and alteration in glucose-stimulated insulin secretion. However, it is not clear whether an increase in uncoupling protein-2 per se induces mitochondrial uncoupling and affects ATP generation and insulin secretion. MATERIALS AND METHODS: Transgenic mice with beta cell-specific overexpression of the human UCP2 gene and INS-1 cells with doxycycline-inducible overproduction of the protein were generated and the consequences of increased levels of UCP2 on glucose-induced insulin secretion and on parameters reflecting mitochondrial uncoupling were determined. RESULTS: In transgenic mice, an increase in beta cell UCP2 protein concentration did not significantly modify plasma glucose and insulin levels. Glucose-induced insulin secretion and elevation in the ATP/ADP ratio were unaltered by an increase in UCP2 level. In INS-1 cells, a similar increase in UCP2 level did not modify glucose-induced insulin secretion, cytosolic ATP and ATP/ADP ratio, or glucose oxidation. Increased levels of UCP2 did not modify the mitochondrial membrane potential and oxygen consumption. Increased UCP2 levels decreased cytokine-induced production of reactive oxygen species. CONCLUSION/INTERPRETATION: The results obtained in transgenic mice and in the beta cell line do not support the hypothesis that an increase in UCP2 protein per se uncouples the mitochondria and decreases glucose-induced insulin secretion. In contrast, the observation that increased UCP2 levels decrease cytokine-induced production of reactive oxygen species indicates a potential protective effect of the protein on beta cells, as observed in other cell types.
Keywords Adenosine Triphosphate/metabolismAnimalsCell LineCell Respiration/physiologyDoxycycline/pharmacologyFemaleGlucose/metabolism/ pharmacologyInsulin/ metabolismInsulin-Secreting Cells/ metabolismIon Channels/genetics/ metabolismMaleMembrane Potential, Mitochondrial/physiologyMiceMice, TransgenicMitochondrial Proteins/genetics/ metabolismReactive Oxygen Species/ metabolism
PMID: 17131143
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PRODUIT-ZENGAFFINEN, Nathalie et al. Increasing uncoupling protein-2 in pancreatic beta cells does not alter glucose-induced insulin secretion but decreases production of reactive oxygen species. In: Diabetologia, 2007, vol. 50, n° 1, p. 84-93. doi: 10.1007/s00125-006-0499-6 https://archive-ouverte.unige.ch/unige:8972

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Deposited on : 2010-07-12

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