Skip to main content
Erschienen in: Diabetologia 12/2009

01.12.2009 | Review

Insights into the critical role of NADPH oxidase(s) in the normal and dysregulated pancreatic beta cell

verfasst von: P. Newsholme, D. Morgan, E. Rebelato, H. C. Oliveira-Emilio, J. Procopio, R. Curi, A. Carpinelli

Erschienen in: Diabetologia | Ausgabe 12/2009

Einloggen, um Zugang zu erhalten

Abstract

It is now widely accepted that reactive oxygen species (ROS) contribute to cell and tissue dysfunction and damage in diabetes. The source of ROS in the insulin secreting pancreatic beta cells has traditionally been considered to be the mitochondrial electron transport chain. While this source is undoubtedly important, we fully describe in this article recent information and evidence of NADPH oxidase-dependent generation of ROS in pancreatic beta cells and identify the various isoforms that contribute to O 2 •− and H2O2 production in various conditions. While glucose-stimulated ROS generation may be important for acute regulation of insulin secretion, at higher levels ROS may disrupt mitochondrial energy metabolism. However, ROS may alter other cellular processes such as signal transduction, ion fluxes and/or cell proliferation/death. The various beta cell isoforms of NADPH oxidase (described in this review) may, via differences in the kinetics and species of ROS generated, positively and negatively regulate insulin secretion and cell survival.
Literatur
1.
Zurück zum Zitat Newsholme P, Brennan L, Bender K (2006) Amino acid metabolism, β-cell function, and diabetes. Diabetes 55(Suppl 2):S39–S47CrossRef Newsholme P, Brennan L, Bender K (2006) Amino acid metabolism, β-cell function, and diabetes. Diabetes 55(Suppl 2):S39–S47CrossRef
2.
Zurück zum Zitat Persaud SJ, Jones PM (1993) The involvement of protein kinase C in glucose stimulated insulin secretion. Biochem Soc Trans 21:428SPubMed Persaud SJ, Jones PM (1993) The involvement of protein kinase C in glucose stimulated insulin secretion. Biochem Soc Trans 21:428SPubMed
3.
Zurück zum Zitat Schrey MP, Montague W (1983) Phosphatidylinositol hydrolysis in isolated guinea-pig islets of Langerhans. Biochem J 216:433–441PubMed Schrey MP, Montague W (1983) Phosphatidylinositol hydrolysis in isolated guinea-pig islets of Langerhans. Biochem J 216:433–441PubMed
4.
Zurück zum Zitat Newsholme P, Keane D, Welters HJ, Morgan NG (2007) Life and death decisions of the pancreatic β-cell: the role of fatty acids. Clin Sci (Lond) 112:27–42CrossRef Newsholme P, Keane D, Welters HJ, Morgan NG (2007) Life and death decisions of the pancreatic β-cell: the role of fatty acids. Clin Sci (Lond) 112:27–42CrossRef
5.
Zurück zum Zitat Metz SA (1988) Membrane phospholipid turnover as an intermediary step in insulin secretion. Putative roles of phospholipases in cell signaling. Am J Med 85:9–21CrossRefPubMed Metz SA (1988) Membrane phospholipid turnover as an intermediary step in insulin secretion. Putative roles of phospholipases in cell signaling. Am J Med 85:9–21CrossRefPubMed
6.
Zurück zum Zitat Jones PM, Persaud SJ (1993) Arachidonic acid as a second messenger in glucose-induced insulin secretion from pancreatic beta-cells. J Endocrinol 137:7–14CrossRefPubMed Jones PM, Persaud SJ (1993) Arachidonic acid as a second messenger in glucose-induced insulin secretion from pancreatic beta-cells. J Endocrinol 137:7–14CrossRefPubMed
7.
Zurück zum Zitat Keane D, Newsholme P (2008) Saturated and unsaturated (including arachidonic acid) non-esterified fatty acid modulation of insulin secretion from pancreatic beta cells. Biochem Soc Trans 36:955–958CrossRefPubMed Keane D, Newsholme P (2008) Saturated and unsaturated (including arachidonic acid) non-esterified fatty acid modulation of insulin secretion from pancreatic beta cells. Biochem Soc Trans 36:955–958CrossRefPubMed
8.
Zurück zum Zitat Metz SA (1988) Exogenous arachidonic acid promotes insulin release from intact or permeabilized rat islets by dual mechanisms. Putative activation of Ca2+ mobilization and protein kinase C. Diabetes 37:1453–1469CrossRefPubMed Metz SA (1988) Exogenous arachidonic acid promotes insulin release from intact or permeabilized rat islets by dual mechanisms. Putative activation of Ca2+ mobilization and protein kinase C. Diabetes 37:1453–1469CrossRefPubMed
9.
Zurück zum Zitat Kruman I, Guo Q, Mattson MP (1998) Calcium and reactive oxygen species mediate staurosporine-induced mitochondrial dysfunction and apoptosis in PC12 cells. J Neurosci Res 51:293–308CrossRefPubMed Kruman I, Guo Q, Mattson MP (1998) Calcium and reactive oxygen species mediate staurosporine-induced mitochondrial dysfunction and apoptosis in PC12 cells. J Neurosci Res 51:293–308CrossRefPubMed
10.
Zurück zum Zitat Yu JH, Kim KH, Kim H (2006) Role of NADPH oxidase and calcium in cerulein-induced apoptosis: involvement of apoptosis-inducing factor. Ann N Y Acad Sci 1090:292–297CrossRefPubMed Yu JH, Kim KH, Kim H (2006) Role of NADPH oxidase and calcium in cerulein-induced apoptosis: involvement of apoptosis-inducing factor. Ann N Y Acad Sci 1090:292–297CrossRefPubMed
11.
Zurück zum Zitat Morgan D, Oliveira-Emilio HR, Keane D et al (2007) Glucose, palmitate and pro-inflammatory cytokines modulate production and activity of a phagocyte-like NADPH oxidase in rat pancreatic islets and a clonal beta cell line. Diabetologia 50:359–369CrossRefPubMed Morgan D, Oliveira-Emilio HR, Keane D et al (2007) Glucose, palmitate and pro-inflammatory cytokines modulate production and activity of a phagocyte-like NADPH oxidase in rat pancreatic islets and a clonal beta cell line. Diabetologia 50:359–369CrossRefPubMed
12.
Zurück zum Zitat Lortz S, Gurgul-Convey E, Lenzen S, Tiedge M (2005) Importance of mitochondrial superoxide dismutase expression in insulin-producing cells for the toxicity of reactive oxygen species and proinflammatory cytokines. Diabetologia 48:1541–1548CrossRefPubMed Lortz S, Gurgul-Convey E, Lenzen S, Tiedge M (2005) Importance of mitochondrial superoxide dismutase expression in insulin-producing cells for the toxicity of reactive oxygen species and proinflammatory cytokines. Diabetologia 48:1541–1548CrossRefPubMed
13.
Zurück zum Zitat Krause KH (2004) Tissue distribution and putative physiological function of NOX family NADPH oxidases. Jpn J Infect Dis 57:S28–S29PubMed Krause KH (2004) Tissue distribution and putative physiological function of NOX family NADPH oxidases. Jpn J Infect Dis 57:S28–S29PubMed
14.
15.
Zurück zum Zitat Borregaard N, Tauber AI (1984) Subcellular localization of the human neutrophil NADPH oxidase b-cytochrome and associated flavoprotein. J Biol Chem 259:47–52PubMed Borregaard N, Tauber AI (1984) Subcellular localization of the human neutrophil NADPH oxidase b-cytochrome and associated flavoprotein. J Biol Chem 259:47–52PubMed
16.
Zurück zum Zitat Vignais PV (2002) The superoxide-generating NADPH oxidase: structural aspects and activation mechanism. Cell Mol Life Sci 59:1428–1459CrossRefPubMed Vignais PV (2002) The superoxide-generating NADPH oxidase: structural aspects and activation mechanism. Cell Mol Life Sci 59:1428–1459CrossRefPubMed
17.
Zurück zum Zitat Lambeth JD, Kawahara T, Diebold B (2007) Regulation of Nox and Duox enzymatic activity and expression. Free Radic Biol Med 43:319–331CrossRefPubMed Lambeth JD, Kawahara T, Diebold B (2007) Regulation of Nox and Duox enzymatic activity and expression. Free Radic Biol Med 43:319–331CrossRefPubMed
18.
Zurück zum Zitat Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313CrossRefPubMed Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313CrossRefPubMed
19.
Zurück zum Zitat Koga H, Terasawa H, Nunoi H, Takeshige K, Inagaki F, Sumimoto H (1999) Tetratricopeptide repeat (TPR) motifs of p67(phox) participate in interaction with the small GTPase Rac and activation of the phagocyte NADPH oxidase. J Biol Chem 274:25051–25060CrossRefPubMed Koga H, Terasawa H, Nunoi H, Takeshige K, Inagaki F, Sumimoto H (1999) Tetratricopeptide repeat (TPR) motifs of p67(phox) participate in interaction with the small GTPase Rac and activation of the phagocyte NADPH oxidase. J Biol Chem 274:25051–25060CrossRefPubMed
20.
Zurück zum Zitat Kawahara T, Quinn MT, Lambeth JD (2007) Molecular evolution of the reactive oxygen-generating NADPH oxidase (Nox/Duox) family of enzymes. BMC Evol Biol 7:109CrossRefPubMed Kawahara T, Quinn MT, Lambeth JD (2007) Molecular evolution of the reactive oxygen-generating NADPH oxidase (Nox/Duox) family of enzymes. BMC Evol Biol 7:109CrossRefPubMed
21.
Zurück zum Zitat Nisimoto Y, Motalebi S, Han CH, Lambeth JD (1999) The p67(phox) activation domain regulates electron flow from NADPH to flavin in flavocytochrome b(558). J Biol Chem 274:22999–23005CrossRefPubMed Nisimoto Y, Motalebi S, Han CH, Lambeth JD (1999) The p67(phox) activation domain regulates electron flow from NADPH to flavin in flavocytochrome b(558). J Biol Chem 274:22999–23005CrossRefPubMed
22.
Zurück zum Zitat Bedard K, Lardy B, Krause KH (2007) NOX family NADPH oxidases: not just in mammals. Biochimie 89:1107–1112CrossRefPubMed Bedard K, Lardy B, Krause KH (2007) NOX family NADPH oxidases: not just in mammals. Biochimie 89:1107–1112CrossRefPubMed
23.
Zurück zum Zitat Oliveira HR, Verlengia R, Carvalho CR, Britto LR, Curi R, Carpinelli AR (2003) Pancreatic beta-cells express phagocyte-like NAD(P)H oxidase. Diabetes 52:1457–1463CrossRefPubMed Oliveira HR, Verlengia R, Carvalho CR, Britto LR, Curi R, Carpinelli AR (2003) Pancreatic beta-cells express phagocyte-like NAD(P)H oxidase. Diabetes 52:1457–1463CrossRefPubMed
24.
Zurück zum Zitat Banfi B, Molnar G, Maturana A et al (2001) A Ca(2+)-activated NADPH oxidase in testis, spleen, lymph nodes. J Biol Chem 276:37594–37601CrossRefPubMed Banfi B, Molnar G, Maturana A et al (2001) A Ca(2+)-activated NADPH oxidase in testis, spleen, lymph nodes. J Biol Chem 276:37594–37601CrossRefPubMed
25.
Zurück zum Zitat Sumimoto H (2008) Structure, regulation and evolution of Nox-family NADPH oxidases that produce reactive oxygen species. FEBS J 275:3249–3277CrossRefPubMed Sumimoto H (2008) Structure, regulation and evolution of Nox-family NADPH oxidases that produce reactive oxygen species. FEBS J 275:3249–3277CrossRefPubMed
26.
Zurück zum Zitat Geiszt M, Leto TL (2004) The NOX family of NAD(P)H oxidases: host defense and beyond. J Biol Chem 279:51715–51718CrossRefPubMed Geiszt M, Leto TL (2004) The NOX family of NAD(P)H oxidases: host defense and beyond. J Biol Chem 279:51715–51718CrossRefPubMed
27.
Zurück zum Zitat Takeya R, Ueno N, Kami K et al (2003) Novel human homologues of p47phox and p67phox participate in activation of superoxide-producing NADPH oxidases. J Biol Chem 278:25234–25246CrossRefPubMed Takeya R, Ueno N, Kami K et al (2003) Novel human homologues of p47phox and p67phox participate in activation of superoxide-producing NADPH oxidases. J Biol Chem 278:25234–25246CrossRefPubMed
28.
Zurück zum Zitat Uchizono Y, Takeya R, Iwase M et al (2006) Expression of isoforms of NADPH oxidase components in rat pancreatic islets. Life Sci 80:133–139CrossRefPubMed Uchizono Y, Takeya R, Iwase M et al (2006) Expression of isoforms of NADPH oxidase components in rat pancreatic islets. Life Sci 80:133–139CrossRefPubMed
29.
Zurück zum Zitat Lapouge K, Smith SJ, Groemping Y, Rittinger K (2002) Architecture of the p40–p47-p67phox complex in the resting state of the NADPH oxidase. A central role for p67phox. J Biol Chem 277:10121–10128CrossRefPubMed Lapouge K, Smith SJ, Groemping Y, Rittinger K (2002) Architecture of the p40–p47-p67phox complex in the resting state of the NADPH oxidase. A central role for p67phox. J Biol Chem 277:10121–10128CrossRefPubMed
30.
Zurück zum Zitat Banfi B, Maturana A, Jaconi S et al (2000) A mammalian H+ channel generated through alternative splicing of the NADPH oxidase homolog NOH-1. Science 287:138–142CrossRefPubMed Banfi B, Maturana A, Jaconi S et al (2000) A mammalian H+ channel generated through alternative splicing of the NADPH oxidase homolog NOH-1. Science 287:138–142CrossRefPubMed
31.
Zurück zum Zitat Sumimoto H, Miyano K, Takeya R (2005) Molecular composition and regulation of the Nox family NAD(P)H oxidases. Biochem Biophys Res Commun 338:677–686CrossRefPubMed Sumimoto H, Miyano K, Takeya R (2005) Molecular composition and regulation of the Nox family NAD(P)H oxidases. Biochem Biophys Res Commun 338:677–686CrossRefPubMed
32.
Zurück zum Zitat Cheng G, Diebold BA, Hughes Y, Lambeth JD (2006) Nox1-dependent reactive oxygen generation is regulated by Rac1. J Biol Chem 281:17718–17726CrossRefPubMed Cheng G, Diebold BA, Hughes Y, Lambeth JD (2006) Nox1-dependent reactive oxygen generation is regulated by Rac1. J Biol Chem 281:17718–17726CrossRefPubMed
33.
Zurück zum Zitat Shiose A, Kuroda J, Tsuruya K et al (2001) A novel superoxide-producing NAD(P)H oxidase in kidney. J Biol Chem 276:1417–1423CrossRefPubMed Shiose A, Kuroda J, Tsuruya K et al (2001) A novel superoxide-producing NAD(P)H oxidase in kidney. J Biol Chem 276:1417–1423CrossRefPubMed
34.
Zurück zum Zitat Kawahara T, Ritsick D, Cheng G, Lambeth JD (2005) Point mutations in the proline-rich region of p22phox are dominant inhibitors of Nox1- and Nox2-dependent reactive oxygen generation. J Biol Chem 280:31859–31869CrossRefPubMed Kawahara T, Ritsick D, Cheng G, Lambeth JD (2005) Point mutations in the proline-rich region of p22phox are dominant inhibitors of Nox1- and Nox2-dependent reactive oxygen generation. J Biol Chem 280:31859–31869CrossRefPubMed
35.
Zurück zum Zitat Martyn KD, Frederick LM, von Loehneysen K, Dinauer MC, Knaus UG (2006) Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases. Cell Signal 18:69–82CrossRefPubMed Martyn KD, Frederick LM, von Loehneysen K, Dinauer MC, Knaus UG (2006) Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases. Cell Signal 18:69–82CrossRefPubMed
36.
Zurück zum Zitat Brandes RP, Schröder K (2008) Composition and functions of vascular nicotinamide adenine dinucleotide phosphate oxidases. Trends Cardiovasc Med 18:15–19CrossRefPubMed Brandes RP, Schröder K (2008) Composition and functions of vascular nicotinamide adenine dinucleotide phosphate oxidases. Trends Cardiovasc Med 18:15–19CrossRefPubMed
37.
Zurück zum Zitat Guichard C, Moreau R, Pessayre D, Epperson TK, Krause KH (2008) NOX family NADPH oxidases in liver and in pancreatic islets: a role in the metabolic syndrome and diabetes. Biochem Soc Trans 36:920–929CrossRefPubMed Guichard C, Moreau R, Pessayre D, Epperson TK, Krause KH (2008) NOX family NADPH oxidases in liver and in pancreatic islets: a role in the metabolic syndrome and diabetes. Biochem Soc Trans 36:920–929CrossRefPubMed
38.
Zurück zum Zitat Schröder K, Wandzioch K, Helmcke I, Brandes RP (2009) Nox4 acts as a switch between differentiation and proliferation in preadipocytes. Arterioscler Thromb Vasc Biol 29:239–245CrossRefPubMed Schröder K, Wandzioch K, Helmcke I, Brandes RP (2009) Nox4 acts as a switch between differentiation and proliferation in preadipocytes. Arterioscler Thromb Vasc Biol 29:239–245CrossRefPubMed
39.
Zurück zum Zitat Mahadev K, Motoshima H, Wu X et al (2004) The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction. Mol Cell Biol 24:1844–1854CrossRefPubMed Mahadev K, Motoshima H, Wu X et al (2004) The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction. Mol Cell Biol 24:1844–1854CrossRefPubMed
40.
Zurück zum Zitat Pi J, Bai Y, Zhang Q et al (2007) Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes 56:1783–1791CrossRefPubMed Pi J, Bai Y, Zhang Q et al (2007) Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes 56:1783–1791CrossRefPubMed
41.
Zurück zum Zitat Morgan D, Rebelato E, Abdulkader F et al (2009) Association of NAD(P)H oxidase with glucose-induced insulin secretion by pancreatic beta cells. Endocrinology 150:2197–2201CrossRefPubMed Morgan D, Rebelato E, Abdulkader F et al (2009) Association of NAD(P)H oxidase with glucose-induced insulin secretion by pancreatic beta cells. Endocrinology 150:2197–2201CrossRefPubMed
42.
Zurück zum Zitat Imoto H, Sasaki N, Iwase M et al (2008) Impaired insulin secretion by diphenyleneiodium associated with perturbation of cytosolic Ca2+ dynamics in pancreatic beta-cells. Endocrinology 149:5391–5400CrossRefPubMed Imoto H, Sasaki N, Iwase M et al (2008) Impaired insulin secretion by diphenyleneiodium associated with perturbation of cytosolic Ca2+ dynamics in pancreatic beta-cells. Endocrinology 149:5391–5400CrossRefPubMed
43.
Zurück zum Zitat Zawalich WS, Zawalich KC (2008) Enhanced activation of phospholipase C and insulin secretion from islets incubated in fatty acid-free bovine serum albumin. Metabolism 57:290–298CrossRefPubMed Zawalich WS, Zawalich KC (2008) Enhanced activation of phospholipase C and insulin secretion from islets incubated in fatty acid-free bovine serum albumin. Metabolism 57:290–298CrossRefPubMed
44.
Zurück zum Zitat Oliveira HR, Curi R, Carpinelli AR (1999) Glucose induces an acute increase of superoxide dismutase activity in incubated rat pancreatic islets. Am J Physiol 276:C507–C510PubMed Oliveira HR, Curi R, Carpinelli AR (1999) Glucose induces an acute increase of superoxide dismutase activity in incubated rat pancreatic islets. Am J Physiol 276:C507–C510PubMed
45.
Zurück zum Zitat Leloup C, Tourrel-Cuzin C, Magnan C et al (2009) Mitochondrial reactive oxygen species are obligatory signals for glucose-induced insulin secretion. Diabetes 58:673–681CrossRefPubMed Leloup C, Tourrel-Cuzin C, Magnan C et al (2009) Mitochondrial reactive oxygen species are obligatory signals for glucose-induced insulin secretion. Diabetes 58:673–681CrossRefPubMed
46.
Zurück zum Zitat Newsholme P, Haber EP, Hirabara SM et al (2007) Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity. J Physiol 583:9–24CrossRefPubMed Newsholme P, Haber EP, Hirabara SM et al (2007) Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity. J Physiol 583:9–24CrossRefPubMed
47.
Zurück zum Zitat Green K, Brand MD, Murphy MP (2004) Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes 53(Suppl 1):S110–S118CrossRefPubMed Green K, Brand MD, Murphy MP (2004) Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes 53(Suppl 1):S110–S118CrossRefPubMed
48.
Zurück zum Zitat Pi J, Bai Y, Daniel K et al (2009) Persistent oxidative stress due to absence of uncoupling protein 2 is associated with impaired pancreatic beta cell function. Endocrinology 150:3040–3048CrossRefPubMed Pi J, Bai Y, Daniel K et al (2009) Persistent oxidative stress due to absence of uncoupling protein 2 is associated with impaired pancreatic beta cell function. Endocrinology 150:3040–3048CrossRefPubMed
49.
Zurück zum Zitat Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine. Oxford University Press, Oxford Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine. Oxford University Press, Oxford
50.
Zurück zum Zitat Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T (1995) Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 270:296–299CrossRefPubMed Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T (1995) Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 270:296–299CrossRefPubMed
51.
Zurück zum Zitat Mahadev K, Zilbering A, Zhu L, Goldstein BJ (2001) Insulin-stimulated hydrogen peroxide reversibly inhibits protein-tyrosine phosphatase 1b in vivo and enhances the early insulin action cascade. J Biol Chem 276:21938–21942CrossRefPubMed Mahadev K, Zilbering A, Zhu L, Goldstein BJ (2001) Insulin-stimulated hydrogen peroxide reversibly inhibits protein-tyrosine phosphatase 1b in vivo and enhances the early insulin action cascade. J Biol Chem 276:21938–21942CrossRefPubMed
52.
Zurück zum Zitat Peskin AV, Winterbourn CC (2006) Taurine chloramine is more selective than hypochlorous acid at targeting critical cysteines and inactivating creatine kinase and glyceraldehyde-3-phosphate dehydrogenase. Free Radic Biol Med 40:45–53CrossRefPubMed Peskin AV, Winterbourn CC (2006) Taurine chloramine is more selective than hypochlorous acid at targeting critical cysteines and inactivating creatine kinase and glyceraldehyde-3-phosphate dehydrogenase. Free Radic Biol Med 40:45–53CrossRefPubMed
53.
Zurück zum Zitat Robertson RP, Zhang HJ, Pyzdrowski KL, Walseth TF (1992) Preservation of insulin mRNA levels and insulin secretion in HIT cells by avoidance of chronic exposure to high glucose concentrations. J Clin Invest 90:320–325CrossRefPubMed Robertson RP, Zhang HJ, Pyzdrowski KL, Walseth TF (1992) Preservation of insulin mRNA levels and insulin secretion in HIT cells by avoidance of chronic exposure to high glucose concentrations. J Clin Invest 90:320–325CrossRefPubMed
54.
Zurück zum Zitat Kaneto H, Katakami N, Kawamori D et al (2007) Involvement of oxidative stress in the pathogenesis of diabetes. Antioxid Redox Signal 9:355–366CrossRefPubMed Kaneto H, Katakami N, Kawamori D et al (2007) Involvement of oxidative stress in the pathogenesis of diabetes. Antioxid Redox Signal 9:355–366CrossRefPubMed
55.
Zurück zum Zitat Kaneto H, Xu G, Fujii N, Kim S, Bonner-Weir S, Weir GC (2002) Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J Biol Chem 277:30010–30018CrossRefPubMed Kaneto H, Xu G, Fujii N, Kim S, Bonner-Weir S, Weir GC (2002) Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J Biol Chem 277:30010–30018CrossRefPubMed
56.
Zurück zum Zitat Kaneto H, Kajimoto Y, Miyagawa J et al (1999) Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes 48:2398–2406CrossRefPubMed Kaneto H, Kajimoto Y, Miyagawa J et al (1999) Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes 48:2398–2406CrossRefPubMed
57.
Zurück zum Zitat Lortz S, Tiedge M, Nachtwey T, Karlsen AE, Nerup J, Lenzen S (2000) Protection of insulin-producing RINm5F cells against cytokine-mediated toxicity through overexpression of antioxidant enzymes. Diabetes 49:1123–1130CrossRefPubMed Lortz S, Tiedge M, Nachtwey T, Karlsen AE, Nerup J, Lenzen S (2000) Protection of insulin-producing RINm5F cells against cytokine-mediated toxicity through overexpression of antioxidant enzymes. Diabetes 49:1123–1130CrossRefPubMed
58.
Zurück zum Zitat Malaisse WJ, Dufrane SP, Mathias PC et al (1985) The coupling of metabolic to secretory events in pancreatic islets. The possible role of glutathione reductase. Biochim Biophys Acta 844:256–264CrossRefPubMed Malaisse WJ, Dufrane SP, Mathias PC et al (1985) The coupling of metabolic to secretory events in pancreatic islets. The possible role of glutathione reductase. Biochim Biophys Acta 844:256–264CrossRefPubMed
59.
Zurück zum Zitat Ammon HP, Mark M (1985) Thiols and pancreatic beta-cell function: a review. Cell Biochem Funct 3:157–171CrossRefPubMed Ammon HP, Mark M (1985) Thiols and pancreatic beta-cell function: a review. Cell Biochem Funct 3:157–171CrossRefPubMed
60.
Zurück zum Zitat Avshalumov MV, Chen BT, Koos T, Tepper JM, Rice ME (2005) Endogenous hydrogen peroxide regulates the excitability of midbrain dopamine neurons via ATP-sensitive potassium channels. J Neurosci 25:4222–4231CrossRefPubMed Avshalumov MV, Chen BT, Koos T, Tepper JM, Rice ME (2005) Endogenous hydrogen peroxide regulates the excitability of midbrain dopamine neurons via ATP-sensitive potassium channels. J Neurosci 25:4222–4231CrossRefPubMed
61.
Zurück zum Zitat Krippeit-Drews P, Kramer C, Welker S, Lang F, Ammon HP, Drews G (1999) Interference of H2O2 with stimulus-secretion coupling in mouse pancreatic beta-cells. J Physiol 514:471–481CrossRefPubMed Krippeit-Drews P, Kramer C, Welker S, Lang F, Ammon HP, Drews G (1999) Interference of H2O2 with stimulus-secretion coupling in mouse pancreatic beta-cells. J Physiol 514:471–481CrossRefPubMed
62.
Zurück zum Zitat Maechler P, Jornot L, Wollheim CB (1999) Hydrogen peroxide alters mitochondrial activation and insulin secretion in pancreatic beta cells. J Biol Chem 274:27905–27913CrossRefPubMed Maechler P, Jornot L, Wollheim CB (1999) Hydrogen peroxide alters mitochondrial activation and insulin secretion in pancreatic beta cells. J Biol Chem 274:27905–27913CrossRefPubMed
63.
Zurück zum Zitat Yan LJ, Levine RL, Sohal RS (1997) Oxidative damage during aging targets mitochondrial aconitase. Proc Natl Acad Sci U S A 94:11168–11172CrossRefPubMed Yan LJ, Levine RL, Sohal RS (1997) Oxidative damage during aging targets mitochondrial aconitase. Proc Natl Acad Sci U S A 94:11168–11172CrossRefPubMed
64.
Zurück zum Zitat Brodie AE, Reed DJ (1987) Reversible oxidation of glyceraldehyde 3-phosphate dehydrogenase thiols in human lung carcinoma cells by hydrogen peroxide. Biochem Biophys Res Commun 148:120–125CrossRefPubMed Brodie AE, Reed DJ (1987) Reversible oxidation of glyceraldehyde 3-phosphate dehydrogenase thiols in human lung carcinoma cells by hydrogen peroxide. Biochem Biophys Res Commun 148:120–125CrossRefPubMed
65.
Zurück zum Zitat Du XL, Edelstein D, Rossetti L et al (2000) Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci U S A 97:12222–12226CrossRefPubMed Du XL, Edelstein D, Rossetti L et al (2000) Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci U S A 97:12222–12226CrossRefPubMed
66.
Zurück zum Zitat Molina y Vedia L, McDonald B, Reep B et al (1992) Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation. J Biol Chem 267:24929–24932PubMed Molina y Vedia L, McDonald B, Reep B et al (1992) Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation. J Biol Chem 267:24929–24932PubMed
67.
Zurück zum Zitat Bulteau AL, Ikeda-Saito M, Szweda LI (2003) Redox-dependent modulation of aconitase activity in intact mitochondria. Biochemistry 42:14846–14855CrossRefPubMed Bulteau AL, Ikeda-Saito M, Szweda LI (2003) Redox-dependent modulation of aconitase activity in intact mitochondria. Biochemistry 42:14846–14855CrossRefPubMed
68.
Zurück zum Zitat Sakai K, Matsumoto K, Nishikawa T et al (2003) Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells. Biochem Biophys Res Commun 300:216–222CrossRefPubMed Sakai K, Matsumoto K, Nishikawa T et al (2003) Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells. Biochem Biophys Res Commun 300:216–222CrossRefPubMed
69.
Zurück zum Zitat Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820CrossRefPubMed Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820CrossRefPubMed
70.
Zurück zum Zitat Martens GA, Cai Y, Hinke S, Stange G, van de Casteele M, Pipeleers D (2005) Glucose suppresses superoxide generation in metabolically responsive pancreatic beta cells. J Biol Chem 280:20389–20396CrossRefPubMed Martens GA, Cai Y, Hinke S, Stange G, van de Casteele M, Pipeleers D (2005) Glucose suppresses superoxide generation in metabolically responsive pancreatic beta cells. J Biol Chem 280:20389–20396CrossRefPubMed
71.
Zurück zum Zitat Bell GI, Polonsky KS (2001) Diabetes mellitus and genetically programmed defects in β-cell function. Nature 414:788–791CrossRefPubMed Bell GI, Polonsky KS (2001) Diabetes mellitus and genetically programmed defects in β-cell function. Nature 414:788–791CrossRefPubMed
72.
Zurück zum Zitat Kahn SE (2003) The relative contributions of insulin resistance and β-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 46:3–19CrossRefPubMed Kahn SE (2003) The relative contributions of insulin resistance and β-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 46:3–19CrossRefPubMed
73.
Zurück zum Zitat Cacicedo JM, Benjachareowong S, Chou E, Ruderman NB, Ido Y (2005) Palmitate-induced apoptosis in cultured bovine retinal pericytes: roles of NAD(P)H oxidase, oxidant stress, and ceramide. Diabetes 54:1838–1845CrossRefPubMed Cacicedo JM, Benjachareowong S, Chou E, Ruderman NB, Ido Y (2005) Palmitate-induced apoptosis in cultured bovine retinal pericytes: roles of NAD(P)H oxidase, oxidant stress, and ceramide. Diabetes 54:1838–1845CrossRefPubMed
74.
Zurück zum Zitat Beeharry N, Chambers JA, Green IC (2004) Fatty acid protection from palmitic acid-induced apoptosis is lost following PI3-kinase inhibition. Apoptosis 9:599–607CrossRefPubMed Beeharry N, Chambers JA, Green IC (2004) Fatty acid protection from palmitic acid-induced apoptosis is lost following PI3-kinase inhibition. Apoptosis 9:599–607CrossRefPubMed
75.
Zurück zum Zitat Pap M, Cooper GM (1998) Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-kinase/Akt cell survival pathway. J Biol Chem 273:19929–19932CrossRefPubMed Pap M, Cooper GM (1998) Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-kinase/Akt cell survival pathway. J Biol Chem 273:19929–19932CrossRefPubMed
76.
Zurück zum Zitat Cardone MH, Roy N, Stennicke HR et al (1998) Regulation of cell death protease caspase-9 by phosphorylation. Science 282:1318–1321CrossRefPubMed Cardone MH, Roy N, Stennicke HR et al (1998) Regulation of cell death protease caspase-9 by phosphorylation. Science 282:1318–1321CrossRefPubMed
77.
Zurück zum Zitat Datta SR, Dudek H, Tao X et al (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91:231–241CrossRefPubMed Datta SR, Dudek H, Tao X et al (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91:231–241CrossRefPubMed
78.
Zurück zum Zitat Donath MY, Gross DJ, Cerasi E, Kaiser N (1999) Hyperglycemia-induced β-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes 48:738–744CrossRefPubMed Donath MY, Gross DJ, Cerasi E, Kaiser N (1999) Hyperglycemia-induced β-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes 48:738–744CrossRefPubMed
79.
Zurück zum Zitat Efanova IB, Zaitsev SV, Zhivotovsky B et al (1998) Glucose and tolbutamide induce apoptosis in pancreatic β-cells. A process dependent on intracellular Ca2+ concentration. J Biol Chem 273:33501–33507CrossRefPubMed Efanova IB, Zaitsev SV, Zhivotovsky B et al (1998) Glucose and tolbutamide induce apoptosis in pancreatic β-cells. A process dependent on intracellular Ca2+ concentration. J Biol Chem 273:33501–33507CrossRefPubMed
80.
81.
Zurück zum Zitat Grover AK, Kwan CY, Samson CE (2003) Effects of peroxynitrite on sarco/endoplasmic reticulum Ca2+ pump isoforms SERCS2b and SERCA3a. Am J Physiol Cell Physiol 285:C1537–C1543PubMed Grover AK, Kwan CY, Samson CE (2003) Effects of peroxynitrite on sarco/endoplasmic reticulum Ca2+ pump isoforms SERCS2b and SERCA3a. Am J Physiol Cell Physiol 285:C1537–C1543PubMed
82.
Zurück zum Zitat Azevedo-Martins AK, Lortz S, Lenzen S, Curi R, Eizirik DL, Tiedge M (2003) Improvement of the mitochondrial antioxidant defense status prevents cytokine-induced nuclear factor-kappaB activation in insulin-producing cells. Diabetes 52:93–101CrossRefPubMed Azevedo-Martins AK, Lortz S, Lenzen S, Curi R, Eizirik DL, Tiedge M (2003) Improvement of the mitochondrial antioxidant defense status prevents cytokine-induced nuclear factor-kappaB activation in insulin-producing cells. Diabetes 52:93–101CrossRefPubMed
83.
Zurück zum Zitat Sekiguchi F, Ishibashi K, Katoh H, Kawamoto Y, Ino T (1990) Genetic profile of alloxan-induced diabetes-susceptible mice (ALS) and resistant mice (ALR). Exp Anim 39:269–272 Sekiguchi F, Ishibashi K, Katoh H, Kawamoto Y, Ino T (1990) Genetic profile of alloxan-induced diabetes-susceptible mice (ALS) and resistant mice (ALR). Exp Anim 39:269–272
84.
Zurück zum Zitat Mathews CE, Leiter EH (1999) Constitutive differences in antioxidant defense status distinguishes alloxan resistant (ALR/Lt) and alloxan susceptible (ALS/Lt) mice. Free Radical Biol Med 27:449–455CrossRef Mathews CE, Leiter EH (1999) Constitutive differences in antioxidant defense status distinguishes alloxan resistant (ALR/Lt) and alloxan susceptible (ALS/Lt) mice. Free Radical Biol Med 27:449–455CrossRef
85.
Zurück zum Zitat Mathews CE, Leiter EH (1999) Resistance of ALR/Lt islets to free radical-mediated diabetogenic stress is inherited as a dominant trait. Diabetes 48:2189–2196CrossRefPubMed Mathews CE, Leiter EH (1999) Resistance of ALR/Lt islets to free radical-mediated diabetogenic stress is inherited as a dominant trait. Diabetes 48:2189–2196CrossRefPubMed
86.
Zurück zum Zitat Mathews CE, Graser R, Savinov A, Serreze DV, Leiter EH (2001) The NOD/Lt-related ALR/Lt strain: unusual resistance of beta cells to autoimmune killing uncovers a role for beta-cell expressed resistance determinants. Proc Natl Acad Sci U S A 98:235–240CrossRefPubMed Mathews CE, Graser R, Savinov A, Serreze DV, Leiter EH (2001) The NOD/Lt-related ALR/Lt strain: unusual resistance of beta cells to autoimmune killing uncovers a role for beta-cell expressed resistance determinants. Proc Natl Acad Sci U S A 98:235–240CrossRefPubMed
87.
Zurück zum Zitat Lenzen S (2008) The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 51:216–226CrossRefPubMed Lenzen S (2008) The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 51:216–226CrossRefPubMed
88.
Zurück zum Zitat Carro E, Torres-Aleman I (2004) The role of insulin and insulin-like growth factor I in the molecular and cellular mechanisms underlying the pathology of Alzheimer’s disease. Eur J Pharmacol 490:127–133CrossRefPubMed Carro E, Torres-Aleman I (2004) The role of insulin and insulin-like growth factor I in the molecular and cellular mechanisms underlying the pathology of Alzheimer’s disease. Eur J Pharmacol 490:127–133CrossRefPubMed
89.
Zurück zum Zitat Zhou J, Zhang S, Zhao X, Wei T (2008) Melatonin impairs NADPH oxidase assembly and decreases superoxide anion production in microglia exposed to amyloid beta 1–42. J Pineal Res 45:157–165CrossRefPubMed Zhou J, Zhang S, Zhao X, Wei T (2008) Melatonin impairs NADPH oxidase assembly and decreases superoxide anion production in microglia exposed to amyloid beta 1–42. J Pineal Res 45:157–165CrossRefPubMed
90.
Zurück zum Zitat Mulder H, Nagorny CLF, Lyssenko V, Groop L (2009) Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene. Diabetologia 52:1240–1249CrossRefPubMed Mulder H, Nagorny CLF, Lyssenko V, Groop L (2009) Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene. Diabetologia 52:1240–1249CrossRefPubMed
Metadaten
Titel
Insights into the critical role of NADPH oxidase(s) in the normal and dysregulated pancreatic beta cell
verfasst von
P. Newsholme
D. Morgan
E. Rebelato
H. C. Oliveira-Emilio
J. Procopio
R. Curi
A. Carpinelli
Publikationsdatum
01.12.2009
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 12/2009
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-009-1536-z

Weitere Artikel der Ausgabe 12/2009

Diabetologia 12/2009 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.