title: Regulation of insulin secretion and reactive oxygen species production by free fatty acids in pancreatic islets.
abstract: Free fatty acids regulate insulin secretion through metabolic and intracellular signaling mechanisms such as induction of malonyl-CoA/long-chain CoA pathway, production of lipids, GPRs (G protein-coupled receptors) activation and the modulation of calcium currents. Fatty acids (FA) are also important inducers of ROS (reactive oxygen species) production in β-cells. Production of ROS for short periods is associated with an increase in GSIS (glucose-stimulated insulin secretion), but excessive or sustained production of ROS is negatively correlated with the insulin secretory process. Several mechanisms for FA modulation of ROS production by pancreatic β-cells have been proposed, such as the control of mitochondrial complexes and electron transport, induction of uncoupling proteins, NADPH oxidase activation, interaction with the renin-angiotensin system, and modulation of the antioxidant defense system. The major sites of superoxide production within mitochondria derive from complexes I and III. The amphiphilic nature of FA favors their incorporation into mitochondrial membranes, altering the membrane fluidity and facilitating the electron leak. The extra-mitochondrial ROS production induced by FA through the NADPH oxidase complex is also an important source of these species in β-cells.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo Sao, Paulo, Brazil. mafe@icb.usp.br
authors.forename: Maria Fernanda Rodrigues
authors.initials: MF
authors.lastname: Graciano
authors.forename: Maíra M R
authors.initials: MM
authors.lastname: Valle
authors.forename: Anjan
authors.initials: A
authors.lastname: Kowluru
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.forename: Angelo R
authors.initials: AR
authors.lastname: Carpinelli
mesh_terms: D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D017382:Reactive Oxygen Species