title: Lipid rather than glucose metabolism is implicated in altered insulin secretion caused by oleate in INS-1 cells.
abstract: A comprehensive metabolic study was carried out to understand how chronic exposure of pancreatic beta-cells to fatty acids causes high basal secretion and 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 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 beta-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).
authors.affiliation: Molecular Nutrition Unit, Department of Nutrition, University of Montreal, Montreal, Quebec, Canada H2L 4M1.
authors.forename: L
authors.initials: L
authors.lastname: Segall
authors.forename: N
authors.initials: N
authors.lastname: Lameloise
authors.forename: F
authors.initials: F
authors.lastname: Assimacopoulos-Jeannet
authors.forename: E
authors.initials: E
authors.lastname: Roche
authors.forename: P
authors.initials: P
authors.lastname: Corkey
authors.forename: S
authors.initials: S
authors.lastname: Thumelin
authors.forename: B E
authors.initials: BE
authors.lastname: Corkey
authors.forename: M
authors.initials: M
authors.lastname: Prentki
mesh_terms: D002460:Cell Line; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D050356:Lipid Metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D007328:Insulin; D019301:Oleic Acid; D005947:Glucose