Association of NAD(P)H Oxidase with Glucose-Induced Insulin Secretion by Pancreatic β-Cells
We previously described the presence of nicotinamide adenine dinucleotide phosphate reduced form [NAD(P)H]oxidase components in pancreatic β-cells and its activation by glucose, palmitic acid, and proinflammatory cytokines. In the present study, the importance of the NAD(P)H oxidase complex for panc...
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creator | Morgan, D Rebelato, E Abdulkader, F Graciano, M. F. R Oliveira-Emilio, H. R Hirata, A. E Rocha, M. S Bordin, S Curi, R Carpinelli, A. R |
description | We previously described the presence of nicotinamide adenine dinucleotide phosphate reduced form [NAD(P)H]oxidase components in pancreatic β-cells and its activation by glucose, palmitic acid, and proinflammatory cytokines. In the present study, the importance of the NAD(P)H oxidase complex for pancreatic β-cell function was examined. Rat pancreatic islets were incubated in the presence of glucose plus diphenyleneiodonium, a NAD(P)H oxidase inhibitor, for 1 h or with the antisense oligonucleotide for p47PHOX during 24 h. Reactive oxygen species (ROS) production was determined by a fluorescence assay using 2,7-dichlorodihydrofluorescein diacetate. Insulin secretion, intracellular calcium responses, [U-14C]glucose oxidation, and expression of glucose transporter-2, glucokinase and insulin genes were examined. Antisense oligonucleotide reduced p47PHOX expression [an important NAD(P)H oxidase cytosolic subunit] and similarly to diphenyleneiodonium also blunted the enzyme activity as indicated by reduction of ROS production. Suppression of NAD(P)H oxidase activity had an inhibitory effect on intracellular calcium responses to glucose and glucose-stimulated insulin secretion by isolated islets. NAD(P)H oxidase inhibition also reduced glucose oxidation and gene expression of glucose transporter-2 and glucokinase. These findings indicate that NAD(P)H oxidase activation plays an important role for ROS production by pancreatic β-cells during glucose-stimulated insulin secretion. The importance of this enzyme complex for the β-cell metabolism and the machinery involved in insulin secretion were also shown.
NAD(P)H oxidase complex might play an important role to control insulin secretion, possibly by modulating glucose metabolism and intracellular calcium homeostasis. |
doi_str_mv | 10.1210/en.2008-1149 |
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NAD(P)H oxidase complex might play an important role to control insulin secretion, possibly by modulating glucose metabolism and intracellular calcium homeostasis.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2008-1149</identifier><identifier>PMID: 19147679</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Chevy Chase, MD: Endocrine Society</publisher><subject>Adenine ; Animals ; Antisense oligonucleotides ; Beta cells ; Biological and medical sciences ; Calcium ; Calcium (intracellular) ; Calcium Signaling - drug effects ; Cell activation ; Cells, Cultured ; Dose-Response Relationship, Drug ; Enzymatic activity ; Enzyme activity ; Enzyme Inhibitors - pharmacology ; Enzymes ; Female ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression Regulation - drug effects ; Glucokinase ; Glucose ; Glucose - metabolism ; Glucose - pharmacology ; Glucose transporter ; Hydrogen Peroxide - metabolism ; Insulin ; Insulin - metabolism ; Insulin Secretion ; Insulin-Secreting Cells - drug effects ; Insulin-Secreting Cells - metabolism ; Intracellular ; NAD(P)H oxidase ; NADPH Oxidases - antagonists & inhibitors ; NADPH Oxidases - genetics ; NADPH Oxidases - physiology ; NADPH-diaphorase ; Nicotinamide ; Nicotinamide adenine dinucleotide ; Onium Compounds - pharmacology ; Oxidase ; Oxidation ; Oxidation-Reduction - drug effects ; Palmitic acid ; Pancreas ; Rats ; Rats, Wistar ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; RNA, Small Interfering - pharmacology ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2009-05, Vol.150 (5), p.2197-2201</ispartof><rights>Copyright © 2009 by The Endocrine Society 2009</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © 2009 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c461t-2baa73c9449479fd2ec78028cb25c150b02d1b19d68f22cbb16eb380a5e4fe713</citedby><cites>FETCH-LOGICAL-c461t-2baa73c9449479fd2ec78028cb25c150b02d1b19d68f22cbb16eb380a5e4fe713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21453240$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19147679$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morgan, D</creatorcontrib><creatorcontrib>Rebelato, E</creatorcontrib><creatorcontrib>Abdulkader, F</creatorcontrib><creatorcontrib>Graciano, M. F. R</creatorcontrib><creatorcontrib>Oliveira-Emilio, H. R</creatorcontrib><creatorcontrib>Hirata, A. E</creatorcontrib><creatorcontrib>Rocha, M. S</creatorcontrib><creatorcontrib>Bordin, S</creatorcontrib><creatorcontrib>Curi, R</creatorcontrib><creatorcontrib>Carpinelli, A. R</creatorcontrib><title>Association of NAD(P)H Oxidase with Glucose-Induced Insulin Secretion by Pancreatic β-Cells</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>We previously described the presence of nicotinamide adenine dinucleotide phosphate reduced form [NAD(P)H]oxidase components in pancreatic β-cells and its activation by glucose, palmitic acid, and proinflammatory cytokines. In the present study, the importance of the NAD(P)H oxidase complex for pancreatic β-cell function was examined. Rat pancreatic islets were incubated in the presence of glucose plus diphenyleneiodonium, a NAD(P)H oxidase inhibitor, for 1 h or with the antisense oligonucleotide for p47PHOX during 24 h. Reactive oxygen species (ROS) production was determined by a fluorescence assay using 2,7-dichlorodihydrofluorescein diacetate. Insulin secretion, intracellular calcium responses, [U-14C]glucose oxidation, and expression of glucose transporter-2, glucokinase and insulin genes were examined. Antisense oligonucleotide reduced p47PHOX expression [an important NAD(P)H oxidase cytosolic subunit] and similarly to diphenyleneiodonium also blunted the enzyme activity as indicated by reduction of ROS production. Suppression of NAD(P)H oxidase activity had an inhibitory effect on intracellular calcium responses to glucose and glucose-stimulated insulin secretion by isolated islets. NAD(P)H oxidase inhibition also reduced glucose oxidation and gene expression of glucose transporter-2 and glucokinase. These findings indicate that NAD(P)H oxidase activation plays an important role for ROS production by pancreatic β-cells during glucose-stimulated insulin secretion. The importance of this enzyme complex for the β-cell metabolism and the machinery involved in insulin secretion were also shown.
NAD(P)H oxidase complex might play an important role to control insulin secretion, possibly by modulating glucose metabolism and intracellular calcium homeostasis.</description><subject>Adenine</subject><subject>Animals</subject><subject>Antisense oligonucleotides</subject><subject>Beta cells</subject><subject>Biological and medical sciences</subject><subject>Calcium</subject><subject>Calcium (intracellular)</subject><subject>Calcium Signaling - drug effects</subject><subject>Cell activation</subject><subject>Cells, Cultured</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzymatic activity</subject><subject>Enzyme activity</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Enzymes</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Glucokinase</subject><subject>Glucose</subject><subject>Glucose - metabolism</subject><subject>Glucose - pharmacology</subject><subject>Glucose transporter</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin Secretion</subject><subject>Insulin-Secreting Cells - drug effects</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Intracellular</subject><subject>NAD(P)H oxidase</subject><subject>NADPH Oxidases - antagonists & inhibitors</subject><subject>NADPH Oxidases - genetics</subject><subject>NADPH Oxidases - physiology</subject><subject>NADPH-diaphorase</subject><subject>Nicotinamide</subject><subject>Nicotinamide adenine dinucleotide</subject><subject>Onium Compounds - pharmacology</subject><subject>Oxidase</subject><subject>Oxidation</subject><subject>Oxidation-Reduction - drug effects</subject><subject>Palmitic acid</subject><subject>Pancreas</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10N1qFDEUB_Agil2rd15LQPwCp-Ykmcnkclm1XSi2oN4JQyZzBqfMJtucHbSv5YP4TGbdwYLoVTjwy_n4M_YYxAlIEG8wnEgh6gJA2ztsAVaXhQEj7rKFEKAKI6U5Yg-IrnKptVb32RFY0KYydsG-LImiH9xuiIHHnn9Yvn15-eqMX3wfOkfIvw27r_x0nHwkLNahmzx2fB1oGofAP6JP-Ptne8MvXchVbuT5zx_FCseRHrJ7vRsJH83vMfv8_t2n1VlxfnG6Xi3PC68r2BWydc4ob7W22ti-k-hNLWTtW1l6KEUrZAct2K6qeyl920KFraqFK1H3aEAds-eHvtsUryekXbMZyOcNXMA4UVMZKKEWVYZP_4JXcUoh79YoUKK0la1MVq8PyqdIlLBvtmnYuHTTgGj2mTcYmn3mzT7zzJ_MTad2g90tnkPO4NkMHHk39iknNdAfJ0GXSmqR3YuDi9P2fyOLeaQ6SAxd9GkIuE1IdHvNPxf9BXwwpSs</recordid><startdate>20090501</startdate><enddate>20090501</enddate><creator>Morgan, D</creator><creator>Rebelato, E</creator><creator>Abdulkader, F</creator><creator>Graciano, M. F. R</creator><creator>Oliveira-Emilio, H. R</creator><creator>Hirata, A. E</creator><creator>Rocha, M. S</creator><creator>Bordin, S</creator><creator>Curi, R</creator><creator>Carpinelli, A. R</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20090501</creationdate><title>Association of NAD(P)H Oxidase with Glucose-Induced Insulin Secretion by Pancreatic β-Cells</title><author>Morgan, D ; Rebelato, E ; Abdulkader, F ; Graciano, M. F. R ; Oliveira-Emilio, H. R ; Hirata, A. E ; Rocha, M. S ; Bordin, S ; Curi, R ; Carpinelli, A. R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c461t-2baa73c9449479fd2ec78028cb25c150b02d1b19d68f22cbb16eb380a5e4fe713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adenine</topic><topic>Animals</topic><topic>Antisense oligonucleotides</topic><topic>Beta cells</topic><topic>Biological and medical sciences</topic><topic>Calcium</topic><topic>Calcium (intracellular)</topic><topic>Calcium Signaling - drug effects</topic><topic>Cell activation</topic><topic>Cells, Cultured</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzymatic activity</topic><topic>Enzyme activity</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Enzymes</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Glucokinase</topic><topic>Glucose</topic><topic>Glucose - metabolism</topic><topic>Glucose - pharmacology</topic><topic>Glucose transporter</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Insulin Secretion</topic><topic>Insulin-Secreting Cells - drug effects</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Intracellular</topic><topic>NAD(P)H oxidase</topic><topic>NADPH Oxidases - antagonists & inhibitors</topic><topic>NADPH Oxidases - genetics</topic><topic>NADPH Oxidases - physiology</topic><topic>NADPH-diaphorase</topic><topic>Nicotinamide</topic><topic>Nicotinamide adenine dinucleotide</topic><topic>Onium Compounds - pharmacology</topic><topic>Oxidase</topic><topic>Oxidation</topic><topic>Oxidation-Reduction - drug effects</topic><topic>Palmitic acid</topic><topic>Pancreas</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morgan, D</creatorcontrib><creatorcontrib>Rebelato, E</creatorcontrib><creatorcontrib>Abdulkader, F</creatorcontrib><creatorcontrib>Graciano, M. 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F. R</au><au>Oliveira-Emilio, H. R</au><au>Hirata, A. E</au><au>Rocha, M. S</au><au>Bordin, S</au><au>Curi, R</au><au>Carpinelli, A. R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of NAD(P)H Oxidase with Glucose-Induced Insulin Secretion by Pancreatic β-Cells</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2009-05-01</date><risdate>2009</risdate><volume>150</volume><issue>5</issue><spage>2197</spage><epage>2201</epage><pages>2197-2201</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>We previously described the presence of nicotinamide adenine dinucleotide phosphate reduced form [NAD(P)H]oxidase components in pancreatic β-cells and its activation by glucose, palmitic acid, and proinflammatory cytokines. In the present study, the importance of the NAD(P)H oxidase complex for pancreatic β-cell function was examined. Rat pancreatic islets were incubated in the presence of glucose plus diphenyleneiodonium, a NAD(P)H oxidase inhibitor, for 1 h or with the antisense oligonucleotide for p47PHOX during 24 h. Reactive oxygen species (ROS) production was determined by a fluorescence assay using 2,7-dichlorodihydrofluorescein diacetate. Insulin secretion, intracellular calcium responses, [U-14C]glucose oxidation, and expression of glucose transporter-2, glucokinase and insulin genes were examined. Antisense oligonucleotide reduced p47PHOX expression [an important NAD(P)H oxidase cytosolic subunit] and similarly to diphenyleneiodonium also blunted the enzyme activity as indicated by reduction of ROS production. Suppression of NAD(P)H oxidase activity had an inhibitory effect on intracellular calcium responses to glucose and glucose-stimulated insulin secretion by isolated islets. NAD(P)H oxidase inhibition also reduced glucose oxidation and gene expression of glucose transporter-2 and glucokinase. These findings indicate that NAD(P)H oxidase activation plays an important role for ROS production by pancreatic β-cells during glucose-stimulated insulin secretion. The importance of this enzyme complex for the β-cell metabolism and the machinery involved in insulin secretion were also shown.
NAD(P)H oxidase complex might play an important role to control insulin secretion, possibly by modulating glucose metabolism and intracellular calcium homeostasis.</abstract><cop>Chevy Chase, MD</cop><pub>Endocrine Society</pub><pmid>19147679</pmid><doi>10.1210/en.2008-1149</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Adenine Animals Antisense oligonucleotides Beta cells Biological and medical sciences Calcium Calcium (intracellular) Calcium Signaling - drug effects Cell activation Cells, Cultured Dose-Response Relationship, Drug Enzymatic activity Enzyme activity Enzyme Inhibitors - pharmacology Enzymes Female Fundamental and applied biological sciences. Psychology Gene expression Gene Expression Regulation - drug effects Glucokinase Glucose Glucose - metabolism Glucose - pharmacology Glucose transporter Hydrogen Peroxide - metabolism Insulin Insulin - metabolism Insulin Secretion Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Intracellular NAD(P)H oxidase NADPH Oxidases - antagonists & inhibitors NADPH Oxidases - genetics NADPH Oxidases - physiology NADPH-diaphorase Nicotinamide Nicotinamide adenine dinucleotide Onium Compounds - pharmacology Oxidase Oxidation Oxidation-Reduction - drug effects Palmitic acid Pancreas Rats Rats, Wistar Reactive oxygen species Reactive Oxygen Species - metabolism RNA, Small Interfering - pharmacology Vertebrates: endocrinology |
title | Association of NAD(P)H Oxidase with Glucose-Induced Insulin Secretion by Pancreatic β-Cells |
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