Assimacopoulos-Jeannet, Uncoupling protein 2: a possible link between fatty acid excess and impaired glucose-induced insulin secretion?, Diabetes 50

The mechanism by which long-term exposure of the b-cell to elevated concentrations of fatty acid alters glucose-induced insulin secretion has been examined. Exposure of INS-1 b-cells to 0.4 mmol/l oleate for 72 h increased basal insulin secretion and decreased insulin release in response to high glucose, but not in response to agents acting at the level of the KATP channel (tolbu-tamide) or beyond (elevated KCl). This also suppressed the glucose-induced increase in the cellular ATP-to-ADP ratio. The depolarization of the plasma membrane pro-moted by glucose was decreased after oleate exposure, whereas the response to KCl was unchanged. Cells exposed to free fatty acids displayed a lower mitochon-drial membrane potential and a decreased glucose-in-duced hyperpolarization. The possible implication o