Lipid rather than glucose metabolism is implicated in altered insulin secretion caused by oleate in INS-1 cells

A comprehensive metabolic study was carried out to understand how chronic e xposure of pancreatic p-cells to fatty acids causes high basal secretion an d impairs glucose-induced insulin release. INS-1 beta-cells were exposed to 0.4 mM oleate for 3 days and subsequently incubated at 5 or 25 mM glucose, after which various parameters were measured. Chronic oleate promoted trig lyceride deposition, increased fatty acid oxidation and esterification, and reduced malonyl-CoA at low glucose in association with elevated basal O-2 consumption and redox state. Oleate caused a modest (25%) reduction in gluc ose oxidation but did not affect glucose usage, the glucose 6-phosphate and citrate contents, and the activity of pyruvate dehydrogenase of INS-1 cell s. Thus changes in glucose metabolism and a Randle-glucose/fatty acid cycle do not explain the altered secretory properties of beta-cells exposed to f atty acids. The main response of INS-1 cells to chronic oleate, which is to increase the oxidation and esterification of fatty acids, may contribute t o cause high basal insulin secretion via increased production of reducing e quivalents and/or the generation of complex lipid messenger molecule(s).