Mitochondrial uncoupling protein-2 is not involved in palmitate-induced impairment of glucose-stimulated insulin secretion in INS-1E insulinoma cells and is not needed for the amplification of insulin release

Biochemistry and Biophysics Reports
Verena Hirschberg Jensen, Charles Affourtit

Abstract

We have recently shown that overnight exposure of INS-1E insulinoma cells to palmitate in the presence of high glucose causes defects in both mitochondrial energy metabolism and glucose-stimulated insulin secretion (GSIS). Here we report experiments designed to test the involvement of mitochondrial uncoupling protein-2 (UCP2) in these glucolipotoxic effects. Measuring real-time oxygen consumption in siRNA-transfected INS-1E cells, we show that deleterious effects of palmitate on the glucose sensitivity of mitochondrial respiration and on the coupling efficiency of oxidative phosphorylation are independent of UCP2. Consistently, palmitate impairs GSIS to the same extent in cells with and without UCP2. Furthermore, we knocked down UCP2 in spheroid INS-1E cell clusters (pseudoislets) to test whether or not UCP2 regulates insulin secretion during prolonged glucose exposure. We demonstrate that there are no differences in temporal GSIS kinetics between perifused pseudoislets with and without UCP2. We conclude that UCP2 is not involved in palmitate-induced impairment of GSIS in INS-1E insulinoma cells and is not needed for the amplification of insulin release. These conclusions inform ongoing debate on the disputed biochemical and ph...Continue Reading

References

Dec 9, 2004·American Journal of Physiology. Endocrinology and Metabolism·Michael J MacDonaldMindy A Kendrick
Jan 22, 2005·Science·Bradford B Lowell, Gerald I Shulman
Jul 12, 2005·Biochimica Et Biophysica Acta·Telma C Esteves, Martin D Brand
Sep 15, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Claire PecqueurCraig B Thompson
Dec 7, 2007·Biochimica Et Biophysica Acta·Tobias NübelFrédéric Bouillaud
Apr 25, 2008·Biochimica Et Biophysica Acta·Charles Affourtit, Martin D Brand
Aug 12, 2008·Biochimica Et Biophysica Acta·Vian AzzuMartin D Brand
Sep 1, 2009·Biochimica Et Biophysica Acta·Vincent PoitoutGhislaine Fontés
Nov 5, 2010·Diabetes, Obesity & Metabolism·M D BrandV Azzu
Nov 5, 2010·Diabetes, Obesity & Metabolism·J Pi, S Collins
Sep 1, 2011·Diabetes Research and Clinical Practice·Jean-Claude Henquin
Jan 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Angelo VozzaGiuseppe Fiermonte

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Methods Mentioned

BETA
transfection
electrophoresis
ELISA
Assay

Software Mentioned

GraphPad Prism
GraphPad

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