NAD(P)H Oxidase Participates in the Palmitate-Induced Superoxide Production and Insulin Secretion by Rat Pancreatic Islets
NAD(P)H Oxidase Participates in the Palmitate-Induced Superoxide Production and Insulin Secretion by Rat Pancreatic Islets
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DOI：
10.1002/jcp.22432
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发表时间：
2011-04-01
影响因子：
5.6
通讯作者：
Carpinelli, Angelo R.
中科院分区：
文献类型：
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作者：
Graciano, Maria Fernanda R.;Santos, Laila R. B.;Carpinelli, Angelo R.
烟酰胺腺嘌呤二核苷酸磷酸[NAD（P）H]氧化酶复合物已被证明参与葡萄糖刺激的胰岛素分泌（GSIS）过程。本研究观察了软脂酸对大鼠胰岛超氧阴离子生成和胰岛素分泌的影响及其机制。将大鼠胰岛与1 mM棕榈酸盐、1%不含脂肪酸的白蛋白、5.6或10 mM葡萄糖一起孵育1小时，并加入NAD（P）H氧化酶（DPI-二亚苯基碘鎓）、PKC（calphostin C）和肉毒碱棕榈酰转移酶-I（CPT-I）（依托莫西）抑制剂。超氧化物含量测定氢乙啶法。棕榈酸盐增加超氧化物的产生在5.6和10 mM葡萄糖的存在下。这种作用依赖于PKC和NAD（P）H氧化酶的激活。棕榈酸氧化被证明有助于在5.6 mM葡萄糖的存在下的超氧化物产生的脂肪酸诱导。事实上，棕榈酸导致p47（PHOX）易位到质膜，如免疫组织化学所示。暴露于棕榈酸1小时上调p47（PHOX）的蛋白质含量和p22（PHOX），gp 91（PHOX），p47（PHOX），胰岛素原和G蛋白偶联受体40（GPR 40）的mRNA水平。脂肪酸刺激胰岛素分泌的存在下，高浓度的葡萄糖减少抑制NAD（P）H氧化酶的活性。总之，NAD（P）H氧化酶是胰岛中超氧化物的重要来源，NAD（P）H氧化酶的活性参与棕榈酸对胰岛素分泌的控制。J.细胞。226：1110-1117，2011。(C)2010 Wiley-Liss，Inc.
Nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase complex has been shown to be involved in the process of glucose-stimulated insulin secretion (GSIS). In this study, we examined the effect of palmitic acid on superoxide production and insulin secretion by rat pancreatic islets and the mechanism involved. Rat pancreatic islets were incubated during 1 h with 1 mM palmitate, 1% fatty acid free-albumin, 5.6 or 10 mM glucose and in the presence of inhibitors of NAD(P)H oxidase (DPI-diphenyleneiodonium), PKC (calphostin C) and carnitine palmitoyl transferase-I (CPT-I) (etomoxir). Superoxide content was determined by hydroethidine assays. Palmitate increased superoxide production in the presence of 5.6 and 10 mM glucose. This effect was dependent on activation of PKC and NAD(P)H oxidase. Palmitic acid oxidation was demonstrated to contribute for the fatty acid induction of superoxide production in the presence of 5.6 mM glucose. In fact, palmitate caused p47(PHOX) translocation to plasma membrane, as shown by immunohistochemistry. Exposure to palmitate for 1 h up-regulated the protein content of p47(PHOX) and the mRNA levels of p22(PHOX), gp91(PHOX), p47(PHOX), proinsulin and the G protein-coupled receptor 40 (GPR40). Fatty acid stimulation of insulin secretion in the presence of high glucose concentration was reduced by inhibition of NAD(P)H oxidase activity. In conclusion, NAD(P)H oxidase is an important source of superoxide in pancreatic islets and the activity of NAD(P)H oxidase is involved in the control of insulin secretion by palmitate. J. Cell. Physiol. 226: 1110-1117, 2011. (C) 2010 Wiley-Liss, Inc.