Genetic modulation of islet β-cell iPLA2β expression provides evidence for its impact on β-cell apoptosis and autophagy

Islets

Volumn 5, Issue 1, 2013, Pages 29-44

  Lei, Xiaoyong ^a   Bone, Robert N ^b   Ali, Tomader ^a   Wohltmann, Mary ^c   Gai, Ying ^a   Goodwin, Karen J ^a   Bohrer, Alan E ^c   Turk, John ^c   Ramanadham, Sasanka ^a  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^b University of Alabama at Birmingham   (United States)

^c Metabolism and Lipid Research   (United States)

Author keywords

Apoptosis; Autophagy; B cell; Caspase 3; Ceramides; IPLA2b; IPLA2B KO; Mitochondrial membrane potential; RIP iPLA2b Tg

Indexed keywords

CALCIUM INDEPENDENT PHOSPHOLIPASE A2; CALCIUM INDEPENDENT PHOSPHOLIPASE A2 BETA; CASPASE 3; CERAMIDE; SPHINGOMYELIN; SPHINGOMYELIN PHOSPHODIESTERASE; THAPSIGARGIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CELL COUNT; CHEMOLUMINESCENCE; CONTROLLED STUDY; DENSITOMETRY; DIABETES MELLITUS; ENDOPLASMIC RETICULUM STRESS; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME DEFICIENCY; FLOW CYTOMETRY; GENETIC REGULATION; GENOTYPE; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; MITOCHONDRIAL MEMBRANE POTENTIAL; MOUSE; NICK END LABELING; NONHUMAN; PANCREAS ISLET BETA CELL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION;

Β-CELL; APOPTOSIS; AUTOPHAGY; CASPASE-3; IPLA2Β; IPLA2Β-KO; MITOCHONDRIAL MEMBRANE POTENTIAL; RIP-IPLA2Β-TG;

ANIMALS; APOPTOSIS; AUTOPHAGY; CASPASE 3; CERAMIDES; DIABETES MELLITUS; ENDOPLASMIC RETICULUM STRESS; ENZYME ACTIVATION; ENZYME INHIBITORS; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GROUP IV PHOSPHOLIPASES A2; INSULIN-SECRETING CELLS; ISLETS OF LANGERHANS; MEMBRANE POTENTIAL, MITOCHONDRIAL; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES; SPHINGOMYELIN PHOSPHODIESTERASE; TISSUE CULTURE TECHNIQUES; UNFOLDED PROTEIN RESPONSE;

EID: 84876231278     PISSN: 19382014     EISSN: 19382022     Source Type: Journal    
DOI: 10.4161/isl.23758     Document Type: Article

References (77)

1. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes 2003; 52:102-10; PMID:12502499; http://dx.doi.org/10.2337/ diabetes.52.1.102.
2. Bernard C, Berthault MF, Saulnier C, Ktorza A. Neogenesis vs. apoptosis As main components of pancreatic β cell ass changes in glucose-infused normal and mildly diabetic adult rats. FASEB J 1999; 13:1195-205; PMID:10385610.
3. Butler AE, Janson J, Soeller WC, Butler PC. Increased β-cell apoptosis prevents adaptive increase in β-cell mass in mouse model of type 2 diabetes: evidence for role of islet amyloid formation rather than direct action of amyloid. Diabetes 2003; 52:2304-14; PMID:12941770; http://dx.doi.org/10.2337/diabetes.52.9.2304.
4. Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 2000; 403:98-103; PMID:10638761; http://dx.doi.org/10.1038/ 47513.
5. Ron D. Translational control in the endoplasmic reticulum stress response. J Clin Invest 2002; 110:1383-8; PMID:12438433.
6. Mehmet H. Caspases find a new place to hide. Nature 2000; 403:29-30; PMID:10638735; http://dx.doi.org/10.1038/47377.
7. Berridge MJ. The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium 2002; 32:235-49; PMID:12543086; http://dx.doi.org/10. 1016/S0143416002001823.
8. Cohen GM. Caspases: the executioners of apoptosis. Biochem J 1997; 326:1-16; PMID:9337844.
9. +-independent phospholipase A2 (iPLA2β) and its role in β-cell programmed cell death. Biochimie 2010; 92:627-37; PMID:20083151; http://dx.doi.org/10.1016/j. biochi.2010.01.005.
10. Gijón MA, Leslie CC. Phospholipases A2. Semin Cell Dev Biol 1997; 8:297-303; PMID:10024493; ttp://dx.doi.org/10.1006/scdb.1997.0151.
11. Gross RW, Ramanadham S, Kruszka KK, Han X, Turk J. Rat and human pancreatic islet cells contain a calcium ion independent phospholipase A2 activity selective for hydrolysis of arachidonate which is stimulated by adenosine triphosphate and is specifically localized to islet beta-cells. Biochemistry 1993; 32:327-36; PMID:8418853; http://dx.doi.org/10.1021/ bi00052a041.
12. Wolf RA, Gross RW. Identification of neutral active phospholipase C which hydrolyzes choline glycerophospholipids and plasmalogen selective phospholipase A2 in canine myocardium. J Biol Chem 1985; 260:7295-303; PMID:3997869.
13. Balsinde J, Pérez R, Balboa MA. Calcium-independent phospholipase A2 and apoptosis. Biochim Biophys Acta 2006; 1761:1344-50; PMID:16962822; http://dx.doi.org/10.1016/j.bbalip.2006.07.013.
14. +-independent phospholipase A2 but not cytosolic phospholipase A2, which undergoes proteolytic inactivation. J Biol Chem 1998; 273:13870-7; PMID:9593733; http://dx.doi.org/ 10.1074/jbc.273.22.13870.
15. + stores and arachidonic acid metabolism. J Clin Invest 1998; 101:1623-32; PMID:9541492; http://dx.doi.org/10.1172/JCI1245.
16. + concentration. Endocrinology 1998; 139:4073-85; PMID:9751485; http://dx.doi.org/10.1210/en.139.10.4073.
17. Ramanadham S, Hsu FF, Bohrer A, Nowatzke W, Ma Z, Turk J. Electrospray ionization mass spectrometric analyses of phospholipids from rat and human pancreatic islets and subcellular membranes: comparison to other tissues and implications for membrane fusion in insulin exocytosis. Biochemistry 1998; 37:4553-67; PMID:9521776; http://dx.doi.org/10.1021/bi9722507.
18. Bao S, Jacobson DA, Wohltmann M, Bohrer A, Jin W, Philipson LH, et al. Glucose homeostasis, insulin secretion, and islet phospholipids in mice that overexpress iPLA2β in pancreatic β-cells and in iPLA2β-null mice. Am J Physiol Endocrinol Metab 2008; 294:E217-29; PMID:17895289; http://dx.doi.org/10.1152/ajpendo.00474.2007.
19. Bao S, Miller DJ, Ma Z, Wohltmann M, Eng G, Ramanadham S, et al. Male mice that do not express group VIA phospholipase A2 produce spermatozoa with impaired motility and have greatly reduced fertility. J Biol Chem 2004; 279:38194-200; PMID:15252026; http://dx.doi.org/10.1074/jbc.M406489200.
20. Lei X, Zhang S, Bohrer A, Bao S, Song H, Ramanadham S. The group VIA calcium-independent phospholipase A2 participates in ER stress-induced INS-1 insulinoma cell apoptosis by promoting ceramide generation via hydrolysis of sphingomyelins by neutral sphingomyelinase. Biochemistry 2007; 46:10170-85; PMID:17685585; http://dx.doi.org/10.1021/bi700017z.
21. Lei X, Zhang S, Barbour SE, Bohrer A, Ford EL, Koizumi A, et al. Spontaneous development of endoplasmic reticulum stress that can lead to diabetes mellitus is associated with higher calcium-independent phospholipase A2 expression: a role for regulation by SREBP-1. J Biol Chem 2010; 285:6693-705; PMID:20032468.
22. Lei X, Zhang S, Bohrer A, Ramanadham S. Calcium-independent phospholipase A2 (iPLA2 β)-mediated ceramide generation plays a key role in the cross-talk between the endoplasmic reticulum (ER) and mitochondria during ER stress-induced insulin-secreting cell apoptosis. J Biol Chem 2008; 283:34819-32; PMID:18936091; http://dx.doi.org/10.1074/jbc.M807409200.
23. Ramanadham S, Hsu FF, Zhang S, Jin C, Bohrer A, Song H, et al. Apoptosis of insulin-secreting cells induced by endoplasmic reticulum stress is amplified by overexpression of group VIA calcium-independent phospholipase A2 (iPLA2 β) and suppressed by inhibition of iPLA2 β. Biochemistry 2004; 43:918-30; PMID:14744135; http://dx.doi.org/10.1021/bi035536m.
24. Lei X, Zhang S, Bohrer A, Barbour SE, Ramanadham S. Role of calcium-independent phospholipase A(2)β in human pancreatic islet β-cell apoptosis. Am J Physiol Endocrinol Metab 2012; 303:E1386-95; PMID:23074238; http://dx.doi.org/10.1152/ajpendo.00234.2012.
25. Choi KS. Autophagy and cancer. Exp Mol Med 2012; 44:109-20; PMID:22257886; http://dx.doi.org/10.3858/emm.2012.44.2.033.
26. Schonthal AH. Targeting endoplasmic reticulum stress for cancer therapy. [Schol Ed]. Front Biosci (Schol Ed) 2012; 4:412-31; PMID:22202068.
27. Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell 2010; 140:313-26; PMID:20144757; http://dx.doi.org/10.1016/j. cell.2010.01.028.
28. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 2012; 8:445-544; PMID:22966490; http://dx.doi.org/10.4161/auto.19496.
29. Tanida I. Autophagosome formation and molecular mechanism of autophagy. Antioxid Redox Signal 2011; 14:2201-14; PMID:20712405; http://dx.doi.org/10. 1089/ars.2010.3482.
30. Yoon KH, Ko SH, Cho JH, Lee JM, Ahn YB, Song KH, et al. Selective β-cell loss and α-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 2003; 88:2300-8; PMID:12727989; http://dx.doi.org/10.1210/jc.2002-020735.
31. Oyadomari S, Takeda K, Takiguchi M, Gotoh T, Matsumoto M, Wada I, et al. Nitric oxide-induced apoptosis in pancreatic beta cells is mediated by the endoplasmic reticulum stress pathway. Proc Natl Acad Sci U S A 2001; 98:10845-50; PMID:11526215; http://dx.doi.org/10.1073/pnas.191207498.
32. Remedi MS, Koster JC, Markova K, Seino S, Miki T, Patton BL, et al. Diet-induced glucose intolerance in mice with decreased beta-cell ATP-sensitive K+ channels. Diabetes 2004; 53:3159-67; PMID:15561946; http://dx.doi.org/10. 2337/diabetes.53.12.3159.
33. Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, et al. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 1997; 275:1129-32; PMID:9027314; http://dx.doi.org/10.1126/science.275.5303. 1129.
34. Seleznev K, Zhao C, Zhang XH, Song K, Ma ZA. Calcium-independent phospholipase A2 localizes in and protects mitochondria during apoptotic induction by staurosporine. J Biol Chem 2006; 281:22275-88; PMID:16728389; http://dx.doi.org/10.1074/jbc.M604330200.
35. Zhao Z, Zhang X, Zhao C, Choi J, Shi J, Song K, et al. Protection of pancreatic beta-cells by group VIA phospholipase A(2)-mediated repair of mitochondrial membrane peroxidation. Endocrinology 2010; 151:3038-48; PMID:20463052; http://dx.doi.org/10.1210/en.2010-0016.
36. Aoto M, Shinzawa K, Suzuki Y, Ohkubo N, Mitsuda N, Tsujimoto Y. Essential role of p38 MAPK in caspase-independent, iPLA(2)-dependent cell death under hypoxia/low glucose conditions. FEBS Lett 2009; 583:1611-8; PMID:19393651; http://dx.doi.org/10.1016/j.febslet.2009.04.028.
37. Kaniuk NA, Kiraly M, Bates H, Vranic M, Volchuk A, Brumell JH. Ubiquitinated-protein aggregates form in pancreatic beta-cells during diabetes-induced oxidative stress and are regulated by autophagy. Diabetes 2007; 56:930-9; PMID:17395740; http://dx.doi.org/10.2337/db06-1160.
38. Choi SE, Lee SM, Lee YJ, Li LJ, Lee SJ, Lee JH, et al. Protective role of autophagy in palmitate-induced INS-1 beta-cell death. Endocrinology 2009; 150:126-34; PMID:18772242; http://dx.doi.org/10.1210/en.2008-0483.
39. Las G, Shirihai OS. The role of autophagy in β-cell lipotoxicity and type 2 diabetes. Diabetes Obes Metab 2010; 12(Suppl 2):15-9; PMID:21029295; http://dx.doi.org/10.1111/j.1463-1326.2010.01268.x.
40. Grasso D, Sacchetti ML, Bruno L, Lo Ré A, Iovanna JL, Gonzalez CD, et al. Autophagy and VMP1 expression are early cellular events in experimental diabetes. Pancreatology 2009; 9:81-8; PMID:19077458; http://dx.doi.org/10.1159/ 000178878.
41. Ebato C, Uchida T, Arakawa M, Komatsu M, Ueno T, Komiya K, et al. Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab 2008; 8:325-32; PMID:18840363; http://dx.doi.org/10.1016/j.cmet.2008.08.009.
42. Tanemura M, Ohmura Y, Deguchi T, Machida T, Tsukamoto R, Wada H, et al. Rapamycin causes upregulation of autophagy and impairs islets function both in vitro and in vivo. Am J Transplant 2012; 12:102-14; PMID:21966953; http://dx.doi.org/10.1111/j.1600-6143.2011.03771.x.
43. Masini M, Lupi R, Bugliani M, Boggi U, Filipponi F, Masiello P, et al. A role for autophagy in β-cell life and death. Islets 2009; 1:157-9; PMID:21099265; http://dx.doi.org/10.4161/isl.1.2.9372.
44. Las G, Serada SB, Wikstrom JD, Twig G, Shirihai OS. Fatty acids suppress autophagic turnover in β-cells. J Biol Chem 2011; 286:42534-44; PMID:21859708; http://dx.doi.org/10.1074/jbc.M111.242412.
45. Fujitani Y, Ebato C, Uchida T, Kawamori R, Watada H. β-cell autophagy: A novel mechanism regulating β-cell function and mass: Lessons from β-cell-specific Atg7-deficient mice. Islets 2009; 1:151-3; PMID:21099263; http://dx.doi.org/10.4161/isl.1.2.9057.
46. Jung HS, Lee MS. Macroautophagy in homeostasis of pancreatic beta-cell. Autophagy 2009; 5:241-3; PMID:19066457; http://dx.doi.org/10.4161/auto.5.2.7518.
47. Jung HS, Chung KW, Won Kim J, Kim J, Komatsu M, Tanaka K, et al. Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. Cell Metab 2008; 8:318-24; PMID:18840362; http://dx.doi.org/10. 1016/j.cmet.2008.08.013.
48. Jung HS, Lee MS. Role of autophagy in diabetes and mitochondria. Ann N Y Acad Sci 2010; 1201:79-83; PMID:20649543; http://dx.doi.org/10.1111/j.1749-6632. 2010.05614.x.
49. Levine B, Yuan J. Autophagy in cell death: an innocent convict? J Clin Invest 2005; 115:2679-88; PMID:16200202; http://dx.doi.org/10.1172/JCI26390.
50. Scarlatti F, Bauvy C, Ventruti A, Sala G, Cluzeaud F, Vandewalle A, et al. Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1. J Biol Chem 2004; 279:18384-91; PMID:14970205; http://dx.doi.org/10.1074/jbc.M313561200.
51. Ganley IG, Wong PM, Jiang X. Thapsigargin distinguishes membrane fusion in the late stages of endocytosis and autophagy. Autophagy 2011; 7:1397-9; PMID:21921693; http://dx.doi.org/10.4161/auto.7.11.17651.
52. Mancuso DJ, Kotzbauer P, Wozniak DF, Sims HF, Jenkins CM, Guan S, et al. Genetic ablation of calcium-independent phospholipase A2γ leads to alterations in hippocampal cardiolipin content and molecular species distribution, mitochondrial degeneration, autophagy, and cognitive dysfunction. J Biol Chem 2009; 284:35632-44; PMID:19840936; http://dx.doi.org/10.1074/jbc. M109.055194.
53. Biancheri R, Rossi A, Alpigiani G, Filocamo M, Gandolfo C, Lorini R, et al. Cerebellar atrophy without cerebellar cortex hyperintensity in infantile neuroaxonal dystrophy (INAD) due to PLA2G6 mutation. Eur J Paediatr Neurol 2007; 11:175-7; PMID:17254819; http://dx.doi.org/10.1016/j.ejpn.2006.11.013.
54. Morgan NV, Westaway SK, Morton JE, Gregory A, Gissen P, Sonek S, et al. PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron. Nat Genet 2006; 38:752-4; PMID:16783378; http://dx.doi.org/10.1038/ng1826.
55. Westaway SK, Gregory A, Hayflick SJ. Mutations in PLA2G6 and the riddle of Schindler disease. J Med Genet 2007; 44:e64; PMID:17209134; http://dx.doi.org/10.1136/jmg.2006.044966.
56. Crompton D, Rehal PK, MacPherson L, Foster K, Lunt P, Hughes I, et al. Multiplex ligation-dependent probe amplification (MLPA) analysis is an effective tool for the detection of novel intragenic PLA2G6 mutations: implications for molecular diagnosis. Mol Genet Metab 2010; 100:207-12; PMID:20226704; http://dx.doi.org/10.1016/j.ymgme.2010.02.009.
57. Hazen SL, Gross RW. Human myocardial cytosolic Ca(2+)-independent phospholipase A2 is modulated by ATP. Concordant ATP-induced alterations in enzyme kinetics and mechanism-based inhibition. Biochem J 1991; 280:581-7; PMID:1764021.
58. + signaling through increased expression of via phospholipase A2 (iPLA2). Am J Physiol Cell Physiol 2011; 300:C542-9; PMID:21178110; http://dx.doi.org/10.1152/ajpcell.00428.2010.
59. Sharma J, Turk J, McHowat J. Endothelial cell prostaglandin I(2) and platelet-activating factor production are markedly attenuated in the calcium-independent phospholipase A(2)β knockout mouse. Biochemistry 2010; 49:5473-81; PMID:20521843; http://dx.doi.org/10.1021/bi100752u.
60. Liu S, Xie Z, Zhao Q, Pang H, Turk J, Calderon L, et al. Smooth muscle-specific expression of calcium-independent phospholipase A2β (iPLA2β) participates in the initiation and early progression of vascular inflammation and neointima formation. J Biol Chem 2012; 287:24739-53; PMID:22637477; http://dx.doi.org/10.1074/jbc.M112.340216.
61. +-independent phospholipase A2 in neutrophils. J Immunol 2010; 184:1507-15; PMID:20053941; http://dx.doi.org/10.4049/jimmunol.0901219.
62. Rahnema P, Shimoni Y, Nygren A. Reduced conduction reserve in the diabetic rat heart: role of iPLA2 activation in the response to ischemia. Am J Physiol Heart Circ Physiol 2011; 300:H326-34; PMID:21037228; http://dx.doi.org/10.1152/ajpheart.00743.2010.
63. Xie Z, Gong MC, Su W, Xie D, Turk J, Guo Z. Role of calcium-independent phospholipase A2β in high glucose-induced activation of RhoA, Rho kinase, and CPI-17 in cultured vascular smooth muscle cells and vascular smooth muscle hypercontractility in diabetic animals. J Biol Chem 2010; 285:8628-38; PMID:20086008; http://dx.doi.org/10.1074/jbc.M109.057711.
64. Kaizer EC, Glaser CL, Chaussabel D, Banchereau J, Pascual V, White PC. Gene expression in peripheral blood mononuclear cells from children with diabetes. J Clin Endocrinol Metab 2007; 92:3705-11; PMID:17595242; http://dx.doi.org/10.1210/jc.2007-0979.
65. Wang X, Jia S, Geoffrey R, Alemzadeh R, Ghosh S, Hessner MJ. Identification of a molecular signature in human type 1 diabetes mellitus using serum and functional genomics. J Immunol 2008; 180:1929-37; PMID:18209091.
66. Kaplan M, Aviram M, Hayek T. Oxidative stress and macrophage foam cell formation during diabetes mellitus-induced atherogenesis: role of insulin therapy. Pharmacol Ther 2012; 136:175-85; PMID:22890211; http://dx.doi.org/10. 1016/j.pharmthera.2012.08.002.
67. Akarte AS, Srinivasan BP, Gandhi S. Vildagliptin selectively ameliorates GLP-1, GLUT4, SREBP-1c mRNA levels and stimulates β-cell proliferation resulting in improved glucose homeostasis in rats with streptozotocin-induced diabetes. J Diabetes Complications 2012; 26:266-74; PMID:22626875; http://dx.doi.org/10.1016/j.jdiacomp.2012.03.013.
68. Chin HJ, Fu YY, Ahn JM, Na KY, Kim YS, Kim S, et al. Omacor, n-3 polyunsaturated fatty acid, attenuated albuminuria and renal dysfunction with decrease of SREBP-1 expression and triglyceride amount in the kidney of type II diabetic animals. Nephrol Dial Transplant 2010; 25:1450-7; PMID:20042400; http://dx.doi.org/10.1093/ndt/gfp695.
69. Heller JJ, Qiu J, Zhou L. Nuclear receptors take center stage in Th17 cell-mediated autoimmunity. J Clin Invest 2011; 121:519-21; PMID:21266768; http://dx.doi.org/10.1172/JCI45939.
70. Wang H, Kouri G, Wollheim CB. ER stress and SREBP-1 activation are implicated in beta-cell glucolipotoxicity. J Cell Sci 2005; 118:3905-15; PMID:16091421; http://dx.doi.org/10.1242/jcs.02513.
71. Boslem E, MacIntosh G, Preston AM, Bartley C, Busch AK, Fuller M, et al. A lipidomic screen of palmitate-treated MIN6 β-cells links sphingolipid metabolites with endoplasmic reticulum (ER) stress and impaired protein trafficking. Biochem J 2011; 435:267-76; PMID:21265737; http://dx.doi.org/10. 1042/BJ20101867.
72. Chan JY, Cooney GJ, Biden TJ, Laybutt DR. Differential regulation of adaptive and apoptotic unfolded protein response signalling by cytokine-induced nitric oxide production in mouse pancreatic beta cells. Diabetologia 2011; 54:1766-76; PMID:21472432; http://dx.doi.org/10.1007/s00125-011-2139-z.
73. Véret J, Coant N, Berdyshev EV, Skobeleva A, Therville N, Bailbé D, et al. Ceramide synthase 4 and de novo production of ceramides with specific N-acyl chain lengths are involved in glucolipotoxicity-induced apoptosis of INS-1 β-cells. Biochem J 2011; 438:177-89; PMID:21592087; http://dx.doi.org/10.1042/BJ20101386.
74. Yano M, Watanabe K, Yamamoto T, Ikeda K, Senokuchi T, Lu M, et al. Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null mice. J Biol Chem 2011; 286:3992-4002; PMID:21115496; http://dx.doi.org/10.1074/jbc.M110.179176.
75. Ma Z, Ramanadham S, Corbett JA, Bohrer A, Gross RW, McDaniel ML, et al. Interleukin-1 enhances pancreatic islet arachidonic acid 12-lipoxygenase product generation by increasing substrate availability through a nitric oxide-dependent mechanism. J Biol Chem 1996; 271:1029-42; PMID:8557627; http://dx.doi.org/10.1074/jbc.271.2.1029.
76. Ramanadham S, Gross RW, Han X, Turk J. Inhibition of arachidonate release by secretagogue-stimulated pancreatic islets suppresses both insulin secretion and the rise in beta-cell cytosolic calcium ion concentration. Biochemistry 1993; 32:337-46; PMID:8418854; http://dx.doi.org/10.1021/bi00052a042.
77. Smelt MJ, Faas MM, de Haan BJ, de Vos P. Pancreatic beta-cell purification by altering FAD and NAD(P)H metabolism. Exp Diab Res 2008; 2008:1-11; http://dx.doi.org/10.1155/2008/165360