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Santos L.R.B. NAD(P)H oxidase Participates in the Oleic Acid-Induced Metabolic Channelling During Insulin Secretion. [Ph.D. thesis (Human Physiology)]. São Paulo: Instituto de Ciências Biomédicas da Universidade de São Paulo; 2010. Fatty acids are required to maintain cellular functioning and are able to modulate glucose stimulated insulin secretion from pancreatic islets. The metabolism of cells is source of reactive oxygen species (ROS) and may be involved in the process of insulin release. The important sites of ROS production are the mitochondria and the NAD(P)H oxidase. The mitochondrial ROS release depends on cellular activity and NAD(P)H oxidase activity depends on many factors, including PKC phosphorylation of p47. Oleic and palmitic acid are the most abundant fatty acids in the circulation. Acute (1 hour) exposure to a physiological concentration of oleic acid (100 μM + 0.1% BSA) induced increased insulin secretion at high glucose concentration. The insulin secretion induced by OA was associated to increased fatty acid oxidation and decreased glucose metabolism. Also, at 16.7 mM glucose, ROS production was increased by OA oxidation through modulation by NAD(P)H oxidase in pancreatic islets. The decreased ROS content induced by NAD(P)H oxidase inhibition induced re-establishment of glucose oxidation after OA stimulus. The relative secretion was stimulated by NAD(P)H oxidase inhibition after OA stimulus. This suggests that ROS produced by NAD(P)H oxidase act as glucose metabolism regulators in the pancreatic β cell after OA stimulus. The consequence of glucose metabolism re-establishment was the insulin secretion raise. In conclusion, oleic acid was able to stimulate glucose induced insulin secretion through NAD(P)H oxidase induced ROS production. The ROS produced by NAD(P)H oxidase acted as regulators of glucose metabolism, that may be more susceptible to regulation by these molecules. The glucose metabolism may be in part responsible for the increased insulin secretion induced by ROS. Key-words: Pancreatic islets. Fatty Acids. Glucose metabolism. NAD(P)H oxidase. Insulin secretion.

Participação da NAD(P)H oxidase no direcionamento do metabolismo induzido pelo ácido oléico durante o processo de secreção de insulina.