Regulation of insulin secretion and production of reactive oxygen species by free fatty acids in pancreatic islets

Islets

Volumn 3, Issue 5, 2011, Pages 213-223

  Rodrigues Graciano, Maria Fernanda ^a   Valle, Maíra M R ^a   Kowluru, Anjan ^b,c   Curi, Rui ^a   Carpinelli, Angelo R ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b WAYNE STATE UNIVERSITY   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

cells; Fatty acids; Hydrogen peroxide; Insulin release; NADPH oxidase; Oxidative stress; Superoxide

Indexed keywords

ACYL COENZYME A; ANTIOXIDANT; FATTY ACID; FLAVINE ADENINE NUCLEOTIDE; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR 40; LACTATE DEHYDROGENASE; LIPID; NICOTINAMIDE ADENINE DINUCLEOTIDE; RAC1 PROTEIN; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SUPEROXIDE; UNCOUPLING PROTEIN; UNCOUPLING PROTEIN 2;

CALCIUM CURRENT; CELL DEATH; ELECTRON TRANSPORT; ENZYME ACTIVATION; ENZYME ACTIVITY; HUMAN; INCUBATION TIME; INSULIN RELEASE; INSULIN SYNTHESIS; MEMBRANE FLUIDITY; MITOCHONDRIAL MEMBRANE; MITOCHONDRION; NONHUMAN; PANCREAS ISLET; REGULATORY MECHANISM; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SIGNAL TRANSDUCTION; UPREGULATION;

ANIMALS; FATTY ACIDS, NONESTERIFIED; HUMANS; INSULIN; INSULIN-SECRETING CELLS; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES;

EID: 80052730999     PISSN: 19382014     EISSN: 19382022     Source Type: Journal    
DOI: 10.4161/isl.3.5.15935     Document Type: Review

References (144)

1. Pi J, Bai Y, Zhang Q, Wong V, Floering LM, Daniel K, et al. Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes 2007; 56:1783-91. (Pubitemid 47025446)
2. 2+ dynamics in pancreatic beta-cells. Endocrinology 2008; 149:5391-400.
3. Morgan D, Rebelato E, Abdulkader F, Graciano MF, Oliveira-Emilio HR, Hirata AE, et al. Association of NAD(P)H oxidase with glucose-induced insulin secretion by pancreatic beta-cells. Endocrinology 2009; 150:2197-201.
4. Graciano MF, Santos LR, Curi R, Carpinelli AR. NAD(P)H oxidase participates in the palmitate-induced superoxide production and insulin secretion by rat pancreatic islets. J Cell Physiol 2010; 226:1110-7.
5. Newsholme P, Haber EP, Hirabara SM, Rebelato EL, Procopio J, Morgan D, et al. Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity. J Physiol (Lond) 2007; 583:9-24. (Pubitemid 47244241)
6. Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes 1991; 40:405-12.
7. Malaisse WJ, Malaisse-Lagae F, Wright PH. Effect of fasting upon insulin secretion in the rat. Am J Physiol 1967; 213:843-8.
8. Boden G, Chen X, Iqbal N. Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetic and nondiabetic subjects. Diabetes 1998; 47:1609-12. (Pubitemid 28445349)
9. Stein DT, Esser V, Stevenson BE, Lane KE, Whiteside JH, Daniels MB, et al. Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat. J Clin Invest 1996; 97:2728-35. (Pubitemid 26197087)
10. Carpinelli AR, Picinato MC, Stevanato E, Oliveira HR, Curi R. Insulin secretion induced by palmitate - a process fully dependent on glucose concentration. Diabetes Metab 2002; 28:37-44.
11. Crespin SR, Greenough WB, 3rd, Steinberg D. Stimulation of insulin secretion by infusion of free fatty acids. J Clin Invest 1969; 48:1934-43.
12. Crespin SR, Greenough WB, Steinberg D. Stimulation of insulin secretion by long-chain free fatty acids. A direct pancreatic effect. J Clin Invest 1973; 52:1979-84.
13. Warnotte C, Gilon P, Nenquin M, Henquin JC. Mechanisms of the stimulation of insulin release by saturated fatty acids. A study of palmitate effects in mouse beta-cells. Diabetes 1994; 43:703-11. (Pubitemid 24138785)
14. Poitout V, Hagman D, Stein R, Artner I, Robertson RP, Harmon JS. Regulation of the insulin gene by glucose and fatty acids. J Nutr 2006; 136:873-6.
15. Wang Y, Wang PY, Takashi K. Chronic effects of different non-esterified fatty acids on pancreatic islets of rats. Endocrine 2006; 29:169-73. (Pubitemid 43780361)
16. Zhou YP, Grill VE. Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle. J Clin Invest 1994; 93:870-6. (Pubitemid 24072831)
17. Prentki M, Joly E, El-Assaad W, Roduit R. Malonyl-CoA signaling, lipid partitioning and glucolipotoxicity: role in beta-cell adaptation and failure in the etiology of diabetes. Diabetes 2002; 51:405-13.
18. Opara EC, Garfinkel M, Hubbard VS, Burch WM, Akwari OE. Effect of fatty acids on insulin release: role of chain length and degree of unsaturation. Am J Physiol 1994; 266:635-9.
19. Stein DT, Stevenson BE, Chester MW, Basit M, Daniels MB, Turley SD, et al. The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation. J Clin Invest 1997; 100:398-403. (Pubitemid 27349087)
20. Morgan NG, Dhayal S. Unsaturated fatty acids as cytoprotective agents in the pancreatic beta-cell. Prostaglandins Leukot Essent Fatty Acids 2010; 82:231-6.
21. Zhou YP, Grill VE. Palmitate-induced beta-cell insensitivity to glucose is coupled to decreased pyruvate dehydrogenase activity and enhanced kinase activity in rat pancreatic islets. Diabetes 1995; 44:394-9.
22. Dobbins RL, Chester MW, Daniels MB, McGarry JD, Stein DT. Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans. Diabetes 1998; 47:1613-8. (Pubitemid 28445350)
23. Berne C. The metabolism of lipids in mouse pancreatic islets. The oxidation of fatty acids and ketone bodies. Biochem J 1975; 152:661-6.
24. Khan A, Ling ZC, Landau BR. Quantifying the carboxylation of pyruvate in pancreatic islets. J Biol Chem 1996; 271:2539-42. (Pubitemid 26047860)
25. MacDonald MJ. Glucose enters mitochondrial metabolism via both carboxylation and decarboxylation of pyruvate in pancreatic islets. Metabolism 1993; 42:1229-31. (Pubitemid 23304794)
26. Sekine N, Cirulli V, Regazzi R, Brown LJ, Gine E, Tamarit-Rodriguez J, et al. Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic beta-cells. Potential role in nutrient sensing. J Biol Chem 1994; 269:4895-902.
27. Farfari S, Schulz V, Corkey B, Prentki M. Glucose-regulated anaplerosis and cataplerosis in pancreatic beta-cells: possible implication of a pyruvate/citrate shuttle in insulin secretion. Diabetes 2000; 49:718-26. (Pubitemid 30339986)
28. Deeney JT, Gromada J, Hoy M, Olsen HL, Rhodes CJ, Prentki M, et al. Acute stimulation with long chain acyl-CoA enhances exocytosis in insulin-secreting cells (HIT T-15 and NMRI beta-cells). J Biol Chem 2000; 275:9363-8. (Pubitemid 30185160)
29. Prentki M, Vischer S, Glennon MC, Regazzi R, Deeney JT, Corkey BE. Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion. J Biol Chem 1992; 267:5802-10.
30. Prentki M, Tornheim K, Corkey BE. Signal transduction mechanisms in nutrient-induced insulin secretion. Diabetologia 1997; 40:32-41.
31. Itoh Y, Kawamata Y, Harada M, Kobayashi M, Fujii R, Fukusumi S, et al. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 2003; 422:173-6. (Pubitemid 36362750)
32. Kebede MA, Alquier T, Latour MG, Poitout V. Lipid receptors and islet function: therapeutic implications? Diabetes Obes Metab 2009; 11:10-20.
33. Briscoe CP, Tadayyon M, Andrews JL, Benson WG, Chambers JK, Eilert MM, et al. The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J Biol Chem 2003; 278:11303-11. (Pubitemid 36792687)
34. Kotarsky K, Nilsson NE, Olde B, Owman C. Progress in methodology. Improved reporter gene assays used to identify ligands acting on orphan seven-transmembrane receptors. Pharmacol Toxicol 2003; 93:249-58. (Pubitemid 38096102)
35. Cartoni C, Yasumatsu K, Ohkuri T, Shigemura N, Yoshida R, Godinot N, et al. Taste preference for fatty acids is mediated by GPR40 and GPR120. J Neurosci 2010; 30:8376-82.
36. Edfalk S, Steneberg P, Edlund H. Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion. Diabetes 2008; 57:2280-7.
37. Parker HE, Habib AM, Rogers GJ, Gribble FM, Reimann F. Nutrient-dependent secretion of glucose-dependent insulinotropic polypeptide from primary murine K cells. Diabetologia 2009; 52:289-98.
38. Latour MG, Alquier T, Oseid E, Tremblay C, Jetton TL, Luo J, et al. GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo. Diabetes 2007; 56:1087-94. (Pubitemid 46525064)
39. Lan H, Hoos LM, Liu L, Tetzloff G, Hu W, Abbondanzo SJ, et al. Lack of FFAR1/GPR40 does not protect mice from high-fat diet-induced metabolic disease. Diabetes 2008; 57:2999-3006.
40. Ogawa T, Hirose H, Miyashita K, Saito I, Saruta T. GPR40 gene Arg211His polymorphism may contribute to the variation of insulin secretory capacity in Japanese men. Metabolism 2005; 54:296-9.
41. Vettor R, Granzotto M, De Stefani D, Trevellin E, Rossato M, Farina MG, et al. Loss-of-function mutation of the GPR40 gene associates with abnormal stimulated insulin secretion by acting on intracellular calcium mobilization. J Clin Endocrinol Metab 2008; 93:3541-50.
42. Martins EF, Miyasaka CK, Newsholme P, Curi R, Carpinelli AR. Changes of fatty acid composition in incubated rat pancreatic islets. Diabetes Metab 2004; 30:21-7. (Pubitemid 38418939)
43. Nolan CJ, Madiraju MS, Delghingaro-Augusto V, Peyot ML, Prentki M. Fatty acid signaling in the {beta}-cell and insulin secretion. Diabetes 2006; 55:16-23.
44. Pappan KL, Pan Z, Kwon G, Marshall CA, Coleman T, Goldberg IJ, et al. Pancreatic beta-cell lipoprotein lipase independently regulates islet glucose metabolism and normal insulin secretion. J Biol Chem 2005; 280:9023-9. (Pubitemid 40409594)
45. Roduit R, Masiello P, Wang SP, Li H, Mitchell GA, Prentki M. A role for hormone-sensitive lipase in glucose-stimulated insulin secretion: a study in hormone- sensitive lipase-deficient mice. Diabetes 2001; 50:1970-5. (Pubitemid 33643662)
46. Winzell MS, Svensson H, Arner P, Ahren B, Holm C. The expression of hormone-sensitive lipase in clonal beta-cells and rat islets is induced by long-term exposure to high glucose. Diabetes 2001; 50:2225-30. (Pubitemid 33641905)
47. Roche E, Farfari S, Witters LA, Assimacopoulos-Jeannet F, Thumelin S, Brun T, et al. Long-term exposure of beta-INS cells to high glucose concentrations increases anaplerosis, lipogenesis and lipogenic gene expression. Diabetes 1998; 47:1086-94. (Pubitemid 28294551)
48. Berthiaume L, Deichaite I, Peseckis S, Resh MD. Regulation of enzymatic activity by active site fatty acylation. A new role for long chain fatty acid acylation of proteins. J Biol Chem 1994; 269:6498-505.
49. Yajima H, Komatsu M, Yamada S, Straub SG, Kaneko T, Sato Y, et al. Cerulenin, an inhibitor of protein acylation, selectively attenuates nutrient stimulation of insulin release: a study in rat pancreatic islets. Diabetes 2000; 49:712-7. (Pubitemid 30339985)
50. Yamada S, Komatsu M, Sato Y, Yamauchi K, Aizawa T, Kojima I. Nutrient modulation of palmitoylated 24-kilodalton protein in rat pancreatic islets. Endocrinology 2003; 144:5232-41. (Pubitemid 37476051)
51. + channel-independent insulinotropic action of glucose. Diabetes 1999; 48:1543-9.
52. 2+ channel and link to insulin release. Am J Physiol Endocrinol Metab 2005; 289:670-7.
53. Shapiro H, Shachar S, Sekler I, Hershfinkel M, Walker MD. Role of GPR40 in fatty acid action on the beta cell line INS-1E. Biochem Biophys Res Commun 2005; 335:97-104. (Pubitemid 41350767)
54. 2+ currents and the size of the readily releasable granule pool in mouse pancreatic beta-cells. J Physiol 2004; 557:935-48.
55. + channels in the insulin-secreting cell line INS-1. Pflugers Arch 2001; 442:49-56.
56. + currents in primary cultured rat pancreatic beta-cells by linoleic acids. Endocrinology 2006; 147:674-82.
57. Newsholme P, Morgan D, Rebelato E, Oliveira-Emilio HC, Procopio J, Curi R, et al. Insights into the critical role of NADPH oxidase(s) in the normal and dysregulated pancreatic beta cell. Diabetologia 2009; 52:2489-98.
58. Kaneto H, Katakami N, Kawamori D, Miyatsuka T, Sakamoto K, Matsuoka TA, et al. Involvement of oxidative stress in the pathogenesis of diabetes. Antioxid Redox Signal 2007; 9:355-66. (Pubitemid 46145981)
59. Igoillo-Esteve M, Marselli L, Cunha DA, Ladriere L, Ortis F, Grieco FA, et al. Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes. Diabetologia 53:1395-405.
60. Abaraviciene SM, Lundquist I, Salehi A. Rosiglitazone counteracts palmitate-induced beta-cell dysfunction by suppression of MAP kinase, inducible nitric oxide synthase and caspase 3 activities. Cell Mol Life Sci 2008; 65:2256-65.
61. Maedler K, Spinas GA, Dyntar D, Moritz W, Kaiser N, Donath MY. Distinct effects of saturated and monounsaturated fatty acids on beta-cell turnover and function. Diabetes 2001; 50:69-76. (Pubitemid 32047983)
62. Karaskov E, Scott C, Zhang L, Teodoro T, Ravazzola M, Volchuk A. Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress, which may contribute to INS-1 pancreatic beta-cell apoptosis. Endocrinology 2006; 147:3398-407.
63. Maestre I, Jordan J, Calvo S, Reig JA, Cena V, Soria B, et al. Mitochondrial dysfunction is involved in apoptosis induced by serum withdrawal and fatty acids in the beta-cell line INS-1. Endocrinology 2003; 144:335-45. (Pubitemid 36076123)
64. Kaneto H, Nakatani Y, Kawamori D, Miyatsuka T, Matsuoka TA, Matsuhisa M, et al. Role of oxidative stress, endoplasmic reticulum stress and c-Jun N-terminal kinase in pancreatic beta-cell dysfunction and insulin resistance. Int J Biochem Cell Biol 2005; 37:1595-608. (Pubitemid 40719639)
65. 2-.), superoxide dismutases and related matters. J Biol Chem 1997; 272:18515-7.
66. Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004; 24:816-23. (Pubitemid 38620857)
67. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 2000; 86:494-501. (Pubitemid 30165039)
68. Victor VM, Apostolova N, Herance R, Hernandez-Mijares A, Rocha M. Oxidative stress and mitochondrial dysfunction in atherosclerosis: mitochondria-targeted antioxidants as potential therapy. Curr Med Chem 2009; 16:4654-67.
69. Harraz MM, Marden JJ, Zhou W, Zhang Y, Williams A, Sharov VS, et al. SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model. J Clin Invest 2008; 118:659-70. (Pubitemid 351206555)
70. Suvorava T, Kojda G. Reactive oxygen species as cardiovascular mediators: lessons from endothelial-specific protein overexpression mouse models. Biochim Biophys Acta 2009; 1787:802-10.
71. Goldstein BJ, Mahadev K, Wu X. Redox paradox: insulin action is facilitated by insulin-stimulated reactive oxygen species with multiple potential signaling targets. Diabetes 2005; 54:311-21.
72. Sivitz WI, Yorek MA. Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxid Redox Signal 2010; 12:537-77.
73. Raha S, Robinson BH. Mitochondria, oxygen free radicals, disease and ageing. Trends Biochem Sci 2000; 25:502-8.
74. Han D, Williams E, Cadenas E. Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space. Biochem J 2001; 353:411-6. (Pubitemid 32096952)
75. Morgan D, Oliveira-Emilio HR, Keane D, Hirata AE, Santos da Rocha M, Bordin S, et al. 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 2007; 50:359-69.
76. Andreyev AY, Kushnareva YE, Starkov AA. Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc) 2005; 70:200-14. (Pubitemid 40512329)
77. Bakker SJ, Ijzerman RG, Teerlink T, Westerhoff HV, Gans RO, Heine RJ. Cytosolic triglycerides and oxidative stress in central obesity: the missing link between excessive atherosclerosis, endothelial dysfunction and beta-cell failure? Atherosclerosis 2000; 148:17-21.
78. Loskovich MV, Grivennikova VG, Cecchini G, Vinogradov AD. Inhibitory effect of palmitate on the mitochondrial NADH:ubiquinone oxidoreductase (complex I) as related to the active-de-active enzyme transition. Biochem J 2005; 387:677-83. (Pubitemid 40685701)
79. Schonfeld P, Wojtczak L. Fatty acids as modulators of the cellular production of reactive oxygen species. Free Radic Biol Med 2008; 45:231-41.
80. Stewart JM, Blakely JA, Johnson MD. The interaction of ferrocytochrome c with long-chain fatty acids and their CoA and carnitine esters. Biochem Cell Biol 2000; 78:675-81. (Pubitemid 32102354)
81. Won JS, Singh I. Sphingolipid signaling and redox regulation. Free Radic Biol Med 2006; 40:1875-88. (Pubitemid 43728861)
82. Wanders RJ, Waterham HR. Biochemistry of mammalian peroxisomes revisited. Annu Rev Biochem 2006; 75:295-332. (Pubitemid 44118035)
83. Gehrmann W, Elsner M, Lenzen S. Role of metabolically generated reactive oxygen species for lipotoxicity in pancreatic beta-cells. Diabetes Obes Metab 2010; 12:149-58.
84. Green K, Brand MD, Murphy MP. Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes 2004; 53:110-8.
85. Zhang CY, Baffy G, Perret P, Krauss S, Peroni O, Grujic D, et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction and type 2 diabetes. Cell 2001; 105:745-55. (Pubitemid 32635104)
86. Rousset S, Mozo J, Dujardin G, Emre Y, Masscheleyn S, Ricquier D, et al. UCP2 is a mitochondrial transporter with an unusual very short half-life. FEBS Lett 2007; 581:479-82. (Pubitemid 46149624)
87. Schrauwen P, Saris WH, Hesselink MK. An alternative function for human uncoupling protein 3: protection of mitochondria against accumulation of nonesterified fatty acids inside the mitochondrial matrix. FASEB J 2001; 15:2497-502. (Pubitemid 33063178)
88. Goglia F, Skulachev VP. A function for novel uncoupling proteins: antioxidant defense of mitochondrial matrix by translocating fatty acid peroxides from the inner to the outer membrane leaflet. FASEB J 2003; 17:1585-91. (Pubitemid 37100060)
89. Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, et al. Superoxide activates mitochondrial uncoupling proteins. Nature 2002; 415:96-9. (Pubitemid 34062457)
90. Echtay KS, Murphy MP, Smith RA, Talbot DA, Brand MD. Superoxide activates mitochondrial uncoupling protein 2 from the matrix side. Studies using targeted antioxidants. J Biol Chem 2002; 277:47129-35. (Pubitemid 36159222)
91. Talbot DA, Duchamp C, Rey B, Hanuise N, Rouanet JL, Sibille B, et al. Uncoupling protein and ATP/ADP carrier increase mitochondrial proton conductance after cold adaptation of king penguins. J Physiol 2004; 558:123-35. (Pubitemid 39077396)
92. Brand MD, Esteves TC. Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3. Cell Metab 2005; 2:85-93.
93. Pi J, Bai Y, Daniel KW, Liu D, Lyght O, Edelstein D, et al. Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic beta-cell function. Endocrinology 2009; 150:3040-8.
94. St-Pierre J, Buckingham JA, Roebuck SJ, Brand MD. Topology of superoxide production from different sites in the mitochondrial electron transport chain. J Biol Chem 2002; 277:44784-90. (Pubitemid 36159072)
95. Koshkin V, Wang X, Scherer PE, Chan CB, Wheeler MB. Mitochondrial functional state in clonal pancreatic beta-cells exposed to free fatty acids. J Biol Chem 2003; 278:19709-15. (Pubitemid 36799156)
96. Brand MD, Affourtit C, Esteves TC, Green K, Lambert AJ, Miwa S, et al. Mitochondrial superoxide: production, biological effects and activation of uncoupling proteins. Free Radic Biol Med 2004; 37:755-67. (Pubitemid 39078548)
97. Joseph JW, Koshkin V, Zhang CY, Wang J, Lowell BB, Chan CB, et al. Uncoupling protein 2 knockout mice have enhanced insulin secretory capacity after a high-fat diet. Diabetes 2002; 51:3211-9. (Pubitemid 35246967)
98. Ruzicka M, Skobisova E, Dlaskova A, Santorova J, Smolkova K, Spacek T, et al. Recruitment of mitochondrial uncoupling protein UCP2 after lipopolysaccharide induction. Int J Biochem Cell Biol 2005; 37:809-21. (Pubitemid 40203002)
99. Medvedev AV, Robidoux J, Bai X, Cao W, Floering LM, Daniel KW, et al. Regulation of the uncoupling protein-2 gene in INS-1 beta-cells by oleic acid. J Biol Chem 2002; 277:42639-44. (Pubitemid 35285632)
100. Surwit RS, Wang S, Petro AE, Sanchis D, Raimbault S, Ricquier D, et al. Diet-induced changes in uncoupling proteins in obesity-prone and obesity-resistant strains of mice. Proc Natl Acad Sci USA 1998; 95:4061-5. (Pubitemid 28173254)
101. Sullivan PG, Rippy NA, Dorenbos K, Concepcion RC, Agarwal AK, Rho JM. The ketogenic diet increases mitochondrial uncoupling protein levels and activity. Ann Neurol 2004; 55:576-80. (Pubitemid 38391976)
102. Sullivan PG, Dube C, Dorenbos K, Steward O, Baram TZ. Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death. Ann Neurol 2003; 53:711-7. (Pubitemid 36622507)
103. Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007; 87:245-313. (Pubitemid 46209993)
104. Oliveira HR, Verlengia R, Carvalho CR, Britto LR, Curi R, Carpinelli AR. Pancreatic beta-cells express phagocyte-like NAD(P)H oxidase. Diabetes 2003; 52:1457-63. (Pubitemid 36666201)
105. Uchizono Y, Takeya R, Iwase M, Sasaki N, Oku M, Imoto H, et al. Expression of isoforms of NADPH oxidase components in rat pancreatic islets. Life Sci 2006; 80:133-9. (Pubitemid 44853977)
106. Vilhardt F, Van Deurs B. The phagocyte NADPH oxidase depends on cholesterol-enriched membrane microdomains for assembly. EMBO J 2004; 23:739-48. (Pubitemid 38418741)
107. Zhang AY, Yi F, Zhang G, Gulbins E, Li PL. Lipid raft clustering and redox signaling platform formation in coronary arterial endothelial cells. Hypertension 2006; 47:74-80. (Pubitemid 43177818)
108. Hilenski LL, Clempus RE, Quinn MT, Lambeth JD, Griendling KK. Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2004; 24:677-83. (Pubitemid 38451603)
109. Cohen AW, Razani B, Schubert W, Williams TM, Wang XB, Iyengar P, et al. Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation. Diabetes 2004; 53:1261-70. (Pubitemid 38569012)
110. Fisher AB. Redox signaling across cell membranes. Antioxid Redox Signal 2009; 11:1349-56.
111. Valle MM, Graciano MF, Lopes de Oliveira ER, Camporez JP, Akamine EH, Carvalho CR, et al. Alterations of NADPH oxidase activity in rat pancreatic islets induced by a high-fat diet. Pancreas 2011; 40:390-5.
112. Mikami A, Imoto K, Tanabe T, Niidome T, Mori Y, Takeshima H, et al. Primary structure and functional expression of the cardiac dihydropyridine- sensitive calcium channel. Nature 1989; 340:230-3. (Pubitemid 19171586)
113. Yuan H, Zhang X, Huang X, Lu Y, Tang W, Man Y, et al. NADPH oxidase 2-derived reactive oxygen species mediate FFAs-induced dysfunction and apoptosis of beta-cells via JNK, p38 MAPK and p53 pathways. PLoS One 5:15726.
114. 2-induced mouse islet or clonal pancreatic beta-cell dysfunction. Biosci Rep 2010; 30:445-53.
115. Keane DC, Takahashi HK, Dhayal S, Morgan NG, Curi R, Newsholme P. Arachidonic acid actions on functional integrity and attenuation of the negative effects of palmitic acid in a clonal pancreatic beta-cell line. Clin Sci (Lond) 2011; 120:195-206.
116. Lau T, Carlsson PO, Leung PS. Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets. Diabetologia 2004; 47:240-8. (Pubitemid 38315360)
117. Leung PS, Chappell MC. A local pancreatic renin-angiotensin system: endocrine and exocrine roles. Int J Biochem Cell Biol 2003; 35:838-46. (Pubitemid 36379325)
118. Leung PS, Carlsson PO. Tissue renin-angiotensin system: its expression, localization, regulation and potential role in the pancreas. J Mol Endocrinol 2001; 26:155-64. (Pubitemid 32514606)
119. Tahmasebi M, Puddefoot JR, Inwang ER, Vinson GP. The tissue renin-angiotensin system in human pancreas. J Endocrinol 1999; 161:317-22. (Pubitemid 29244259)
120. Carlsson PO, Berne C, Jansson L. Angiotensin II and the endocrine pancreas: effects on islet blood flow and insulin secretion in rats. Diabetologia 1998; 41:127-33. (Pubitemid 28088387)
121. Hirata AE, Morgan D, Oliveira-Emilio HR, Rocha MS, Carvalho CR, Curi R, et al. Angiotensin II induces superoxide generation via NAD(P)H oxidase activation in isolated rat pancreatic islets. Regul Pept 2009; 153:1-6.
122. Lupi R, Del Guerra S, Bugliani M, Boggi U, Mosca F, Torri S, et al. The direct effects of the angiotensin-converting enzyme inhibitors, zofenoprilat and enalaprilat, on isolated human pancreatic islets. Eur J Endocrinol 2006; 154:355-61.
123. Chu KY, Lau T, Carlsson PO, Leung PS. Angiotensin II type 1 receptor blockade improves beta-cell function and glucose tolerance in a mouse model of type 2 diabetes. Diabetes 2006; 55:367-74. (Pubitemid 43343265)
124. Nakayama M, Inoguchi T, Sonta T, Maeda Y, Sasaki S, Sawada F, et al. Increased expression of NAD(P)H oxidase in islets of animal models of Type 2 diabetes and its improvement by an AT1 receptor antagonist. Biochem Biophys Res Commun 2005; 332:927-33. (Pubitemid 40798176)
125. Vitale C, Mercuro G, Castiglioni C, Cornoldi A, Tulli A, Fini M, et al. Metabolic effect of telmisartan and losartan in hypertensive patients with metabolic syndrome. Cardiovasc Diabetol 2005; 4:1-8.
126. Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Desai P, Pravenec M, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. Hypertension 2004; 43:993-1002. (Pubitemid 38579904)
127. Tikellis C, Wookey PJ, Candido R, Andrikopoulos S, Thomas MC, Cooper ME. Improved islet morphology after blockade of the rennin-angiotensin system in the ZDF rat. Diabetes 2004; 53:989-97. (Pubitemid 38436611)
128. Saitoh Y, Hongwei W, Ueno H, Mizuta M, Nakazato M. Telmisartan attenuates fatty-acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells. Diabetes Metab 2009; 35:392-7.
129. Saitoh Y, Hongwei W, Ueno H, Mizuta M, Nakazato M. Candesartan attenuates fatty acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells. Diabetes Res Clin Pract 2010; 90:54-9.
130. Veluthakal R, Madathilparambil SV, McDonald P, Olson LK, Kowluru A. Regulatory roles for Tiam1, a guanine nucleotide exchange factor for Rac1, in glucose-stimulated insulin secretion in pancreatic beta-cells. Biochem Pharmacol 2009; 77:101-13.
131. Mertens AE, Roovers RC, Collard JG. Regulation of Tiam1-Rac signalling. FEBS Lett 2003; 546:11-6. (Pubitemid 36782277)
132. Syed I, Jayaram B, Subasinghe W, Kowluru A. Tiam1/Rac1 signaling pathway mediates palmitate-induced, ceramide-sensitive generation of superoxides and lipid peroxides and the loss of mitochondrial membrane potential in pancreatic beta-cells. Biochem Pharmacol 2010; 80:874-83.
133. Grankvist K, Marklund SL, Taljedal IB. CuZn-superoxide dismutase, Mn-superoxide dismutase, catalase and glutathione peroxidase in pancreatic islets and other tissues in the mouse. Biochem J 1981; 199:393-8. (Pubitemid 12216744)
134. Lenzen S, Drinkgern J, Tiedge M. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radic Biol Med 1996; 20:463-6. (Pubitemid 26077870)
135. Tiedge M, Lortz S, Drinkgern J, Lenzen S. Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 1997; 46:1733-42. (Pubitemid 27456404)
136. Tran PO, Parker SM, LeRoy E, Franklin CC, Kavanagh TJ, Zhang T, et al. Adenoviral overexpression of the glutamylcysteine ligase catalytic subunit protects pancreatic islets against oxidative stress. J Biol Chem 2004; 279:53988-93. (Pubitemid 40053130)
137. Rashidi A, Kirkwood TB, Shanley DP. Metabolic evolution suggests an explanation for the weakness of antioxidant defences in beta-cells. Mech Ageing Dev 2009; 130:216-21.
138. Tonooka N, Oseid E, Zhou H, Harmon JS, Robertson RP. Glutathione peroxidase protein expression and activity in human islets isolated for transplantation. Clin Transplant 2007; 21:767-72. (Pubitemid 350056146)
139. Cornelius JG, Luttge BG, Peck AB. Antioxidant enzyme activities in IDD-prone and IDD-resistant mice: a comparative study. Free Radic Biol Med 1993; 14:409-20. (Pubitemid 23087404)
140. Ladyman SR, Augustine RA, Grattan DR. Hormone interactions regulating energy balance during pregnancy. J Neuroendocrinol 2010; 22:805-17.
141. Fehm HL, Kern W, Peters A. The selfish brain: competition for energy resources. Prog Brain Res 2006; 153:129-40. (Pubitemid 44107413)
142. Rebelato E, Abdulkader F, Curi R, Carpinelli AR. Low doses of hydrogen peroxide impair glucose-stimulated insulin secretion via inhibition of glucose metabolism and intracellular calcium oscillations. Metabolism 2010; 59:409-13.
143. Vandewalle B, Moerman E, Lefebvre B, Defrance F, Gmyr V, Lukowiak B, et al. PPARgamma-dependent and -independent effects of rosiglitazone on lipotoxic human pancreatic islets. Biochem Biophys Res Commun 2008; 366:1096-101.
144. Bikopoulos G, Da Silva Pimenta A, Lee SC, Lakey JR, Der SD, Chan CB, et al. Ex vivo transcriptional profiling of human pancreatic islets following chronic exposure to monounsaturated fatty acids. J Endocrinol 2008; 196:455-64. (Pubitemid 351425501)