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Sodium Palmitate Induces Partial Mitochondrial Uncoupling and Reactive Oxygen Species in Rat Pancreatic Islets in Vitro¹

Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden

Address all correspondence and requests for reprints to: Dr. Nils Welsh, Department of Medical Cell Biology, Biomedical Center, P.O. Box 571, S-751 23 Uppsala, Sweden. E-mail: nils.welsh{at}medcellbiol.uu.se

The aim of the present investigation was to study whether prolonged exposure of isolated rat islets to the long chain fatty acid sodium palmitate leads to uncoupling of respiration. It was found that culture of islets in the presence of palmitate abolished glucose-sensitive insulin release and decreased insulin contents. This was paralleled by decreased ATP contents, increased respiration, and decreased islet cell mitochondrial membrane potential. Using electron microscopy, an increase in the ß-cell mitochondrial volume in islets exposed to palmitate was observed. The addition of the uncoupler carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone, at a concentration that decreased mitochondrial membrane potential to a similar extent as palmitate, diminished the glucose-induced insulin release. In addition, islet generation of reactive oxygen species, but not of nitric oxide, was increased in response to a long-term palmitate exposure. It is concluded that long-term exposure to a long chain fatty acid induces partial uncoupling of ß-cell oxidative phosphorylation and that this may contribute to the loss of glucose-sensitive insulin release.

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