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

Article Article scientifique Article Increasing uncoupling protein-2 in pancreatic beta cells does not alter glucose-induced insulin secretion but decreases production of reactive oxygen species eng 2006-11-28 2007-01 author Produit-Zengaffinen Nathalie 506189 author Davis-Lameloise N. author Perreten H. author Becard D. author Gjinovci Aslan 26086 author Keller Patrick Alexandre 81595 author Wollheim Claes 25195 author Herrera Pedro Luis 0000-0003-0771-9504 23981 author Muzzin Patrick 23003 author Assimacopoulos Françoise 26365 84-93 10.1007/s00125-006-0499-6 17131143 0012-186X http://www.springerlink.com/content/481h8233147x30t7/fulltext.pdf 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. Adenosine Triphosphate/metabolism Animals Cell Line Cell Respiration/physiology Doxycycline/pharmacology Female Glucose/metabolism/ pharmacology Insulin/ metabolism Insulin-Secreting Cells/ metabolism Ion Channels/genetics/ metabolism Male Membrane Potential, Mitochondrial/physiology Mice Mice, Transgenic Mitochondrial Proteins/genetics/ metabolism Reactive Oxygen Species/ metabolism Dewey 616 Swiss National Science Foundation 32.63624.00 56 Département de médecine 221 false 272 Types cellulaires pancréatiques pendant l'ontogénèse 522 Diabetologia 50 1 6b427398-9908-4780-bd49-f5506f732ef9 Article (Published version) Public file1.pdf 282223 application/pdf 353bc774-6aca-42c2-92ca-05ea1fad5b58 Supplemental data Public 125_2006_499_MOESM1_ESM.doc 33280 application/msword Table 1: Plasma and pancreatic parameters of control and RIP-UCP2 transgenic mice (L233) b3316c4e77b90cd24d9b6fb0c2a74b24d413c9c8c2d30b76db58ff88c5ccad5b 01fa8bf2-6412-4aac-bc26-07fb2104f6a9 Appendix Public 125_2006_499_MOESM2_ESM.doc 98992 application/msword Figure 1 fe68bdc07038473231540cbaa0cf6ed187a5b16562f6ac16954083b6685d95c8 openAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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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	Diabetologia			2007	739	271

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Keller, Patrick Alexandre