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

• Published in: American journal of physiology: endocrinology and metabolism 1999-09, Vol.277 (3), p.E521-E528
• Main Authors: Segall, Laura, Lameloise, Nathalie, Assimacopoulos-Jeannet, Francoise, Roche, Enrique, Corkey, Pamela, Thumelin, Stephane, Corkey, Barbara E, Prentki, Marc
• Format: Article
• Language: English
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.1999.277.3.e521

1  Molecular Nutrition Unit, Department of Nutrition, University of Montreal, and the Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer, Montreal, Quebec, Canada H2L 4M1; 2  Department of Medical Biochemistry, Centre Médical Universitaire, University of Geneva, Geneva, Switzerland 1211; and 3  Center for Obesity and Metabolism at Boston University Medical Center, Boston University Medical School, Boston, Massachussets 02118 A comprehensive metabolic study was carried out to understand how chronic exposure of pancreatic -cells to fatty acids causes high basal secretion and impairs glucose-induced insulin release. INS-1 -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 triglyceride 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 glucose oxidation but did not affect glucose usage, the glucose 6-phosphate and citrate contents, and the activity of pyruvate dehydrogenase of INS-1 cells. Thus changes in glucose metabolism and a Randle-glucose/fatty acid cycle do not explain the altered secretory properties of -cells exposed to fatty acids. The main response of INS-1 cells to chronic oleate, which is to increase the oxidation and esterification of fatty acids, may contribute to cause high basal insulin secretion via increased production of reducing equivalents and/or the generation of complex lipid messenger molecule(s). fatty acids; insulin secretion; obesity; type 2 diabetes