{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:13:57Z","timestamp":1786979637912,"version":"build-2736575974"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2015,3,26]],"date-time":"2015-03-26T00:00:00Z","timestamp":1427328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2015,6]]},"DOI":"10.1007\/s00125-015-3563-2","type":"journal-article","created":{"date-parts":[[2015,3,25]],"date-time":"2015-03-25T22:22:17Z","timestamp":1427322137000},"page":"1260-1271","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["The p66Shc redox adaptor protein is induced by saturated fatty acids and mediates lipotoxicity-induced apoptosis in pancreatic beta cells"],"prefix":"10.1007","volume":"58","author":[{"given":"Annalisa","family":"Natalicchio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Tortosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Labarbuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Biondi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Marrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Carchia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Leonardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Cignarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Bugliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Marchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Paolo","family":"Fadini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Giorgio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Avogaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastio","family":"Perrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Laviola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Giorgino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,3,26]]},"reference":[{"key":"3563_CR1","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1007\/BF00422371","volume":"38","author":"G Paolisso","year":"1995","unstructured":"Paolisso G, Tataranni PA (1995) A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia 38:1213\u20131217","journal-title":"Diabetologia"},{"key":"3563_CR2","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1073\/pnas.95.5.2498","volume":"95","author":"M Shimabukuro","year":"1998","unstructured":"Shimabukuro M, Zhou YT, Levi M, Unger RH (1998) Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes. Proc Natl Acad Sci U S A 95:2498\u20132502","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3563_CR3","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1007\/s001250051130","volume":"42","author":"JD McGarry","year":"1999","unstructured":"McGarry JD, Dobbins RL (1999) Fatty acids, lipotoxicity and insulin secretion. Diabetologia 42:128\u2013138","journal-title":"Diabetologia"},{"issue":"Pt 14","key":"3563_CR4","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1242\/jcs.026062","volume":"121","author":"DA Cunha","year":"2008","unstructured":"Cunha DA, Hekerman P, Ladri\u00e8re L et al (2008) Initiation and execution of lipotoxic ER stress in pancreatic beta cells. J Cell Sci 121(Pt 14):2308\u20132318","journal-title":"J Cell Sci"},{"key":"3563_CR5","doi-asserted-by":"crossref","first-page":"803","DOI":"10.2337\/diabetes.50.4.803","volume":"50","author":"N Lameloise","year":"2001","unstructured":"Lameloise N, Muzzin P, Prentki M, Assimacopoulos-Jeannet F (2001) Uncoupling protein 2: a possible link between fatty acid excess and impaired glucose-induced insulin secretion? Diabetes 50:803\u2013809","journal-title":"Diabetes"},{"key":"3563_CR6","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1007\/s00125-013-3028-4","volume":"56","author":"A Natalicchio","year":"2013","unstructured":"Natalicchio A, Labarbuta R, Tortosa F et al (2013) Exendin-4 protects pancreatic beta cells from palmitate-induced apoptosis by interfering with GPR40 and the MKK4\/7 stress kinase signalling pathway. Diabetologia 56:2456\u20132466","journal-title":"Diabetologia"},{"key":"3563_CR7","doi-asserted-by":"crossref","first-page":"e15726","DOI":"10.1371\/journal.pone.0015726","volume":"5","author":"H Yuan","year":"2010","unstructured":"Yuan H, Zhang X, Huang X et al (2010) NADPH oxidase 2-derived reactive oxygen species mediate FFAs-induced dysfunction and apoptosis of \u03b2-cells via JNK, p38 MAPK and p53 pathways. PLoS One 5:e15726","journal-title":"PLoS One"},{"key":"3563_CR8","doi-asserted-by":"crossref","first-page":"991","DOI":"10.2337\/diabetes.52.4.991","volume":"52","author":"K Eitel","year":"2003","unstructured":"Eitel K, Staiger H, Rieger J et al (2003) Protein kinase C delta activation and translocation to the nucleus are required for fatty acid-induced apoptosis of insulin-secreting cells. Diabetes 52:991\u2013997","journal-title":"Diabetes"},{"issue":"Suppl 2","key":"3563_CR9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1463-1326.2010.01265.x","volume":"12","author":"W Gehrmann","year":"2010","unstructured":"Gehrmann W, Elsner M, Lenzen S (2010) Role of metabolically generated reactive oxygen species for lipotoxicity in pancreatic \u03b2-cells. Diabetes Obes Metab 12(Suppl 2):149\u2013158","journal-title":"Diabetes Obes Metab"},{"key":"3563_CR10","doi-asserted-by":"crossref","first-page":"49676","DOI":"10.1074\/jbc.M208756200","volume":"277","author":"CE Wrede","year":"2002","unstructured":"Wrede CE, Dickson LM, Lingohr MK, Briaud I, Rhodes CJ (2002) Protein kinase B\/Akt prevents fatty acid-induced apoptosis in pancreatic beta cells (INS-1). J Biol Chem 277:49676\u201349684","journal-title":"J Biol Chem"},{"key":"3563_CR11","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/S0959-437X(00)00146-5","volume":"10","author":"L Luzi","year":"2000","unstructured":"Luzi L, Confalonieri S, Di Fiore PP, Pelicci PG (2000) Evolution of Shc functions from nematode to human. Curr Opin Genet Dev 10:668\u2013674","journal-title":"Curr Opin Genet Dev"},{"key":"3563_CR12","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3109\/13813455.2011.562513","volume":"117","author":"A Natalicchio","year":"2011","unstructured":"Natalicchio A, Tortosa F, Perrini S, Laviola L, Giorgino F (2011) p66Shc, a multifaceted protein linking Erk signalling, glucose metabolism, and oxidative stress. Arch Physiol Biochem 117:116\u2013124","journal-title":"Arch Physiol Biochem"},{"key":"3563_CR13","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/emboj\/16.4.706","volume":"16","author":"E Migliaccio","year":"1997","unstructured":"Migliaccio E, Mele S, Salcini AE et al (1997) Opposite effects of the p52shc\/p46shc and p66shc splicing isoforms on the EGF receptor-MAP kinase-fos signalling pathway. EMBO J 16:706\u2013716","journal-title":"EMBO J"},{"key":"3563_CR14","doi-asserted-by":"crossref","first-page":"28042","DOI":"10.1074\/jbc.272.44.28042","volume":"272","author":"S Okada","year":"1997","unstructured":"Okada S, Kao AW, Ceresa BP, Blaikie P, Margolis B, Pessin JE (1997) The 66-kDa Shc isoform is a negative regulator of the epidermal growth factor-stimulated mitogen-activated protein kinase pathway. J Biol Chem 272:28042\u201328049","journal-title":"J Biol Chem"},{"key":"3563_CR15","doi-asserted-by":"crossref","first-page":"6110","DOI":"10.1074\/jbc.M708799200","volume":"283","author":"I Arany","year":"2008","unstructured":"Arany I, Faisal A, Nagamine Y, Safirstein RL (2008) p66shc inhibits pro-survival epidermal growth factor receptor\/ ERK signaling during severe oxidative stress in mouse renal proximal tubule cells. J Biol Chem 283:6110\u20136117","journal-title":"J Biol Chem"},{"key":"3563_CR16","doi-asserted-by":"crossref","first-page":"43900","DOI":"10.1074\/jbc.M403936200","volume":"279","author":"A Natalicchio","year":"2004","unstructured":"Natalicchio A, Laviola L, de Tullio C (2004) Role of the p66Shc isoform in insulin-like growth factor I receptor signaling through MEK\/Erk and regulation of actin cytoskeleton in rat myoblasts. J Biol Chem 279:43900\u201343909","journal-title":"J Biol Chem"},{"key":"3563_CR17","doi-asserted-by":"crossref","first-page":"E228","DOI":"10.1152\/ajpendo.90347.2008","volume":"296","author":"A Natalicchio","year":"2009","unstructured":"Natalicchio A, de Stefano F, Perrini S et al (2009) Involvement of the p66Shc protein in glucose transport regulation in skeletal muscle myoblasts. Am J Physiol Endocrinol Metab 296:E228\u2013E237","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"3563_CR18","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/46311","volume":"402","author":"E Migliaccio","year":"1999","unstructured":"Migliaccio E, Giorgio M, Mele S et al (1999) The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402:309\u2013313","journal-title":"Nature"},{"key":"3563_CR19","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.2337\/db05-1477","volume":"55","author":"S Menini","year":"2006","unstructured":"Menini S, Amadio L, Oddi G et al (2006) Deletion of p66Shc longevity gene protects against experimental diabetic glomerulopathy by preventing diabetes-induced oxidative stress. Diabetes 55:1642\u20131650","journal-title":"Diabetes"},{"key":"3563_CR20","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.2337\/db13-0894","volume":"63","author":"M Albiero","year":"2014","unstructured":"Albiero M, Poncina N, Tjwa M et al (2014) Diabetes causes bone marrow autonomic neuropathy and impairs stem cell mobilization via dysregulated p66Shc and Sirt1. Diabetes 63:1353\u20131365","journal-title":"Diabetes"},{"key":"3563_CR21","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1210\/jc.2004-1283","volume":"90","author":"E Pagnin","year":"2005","unstructured":"Pagnin E, Fadini G, de Toni R, Tiengo A, Cal\u00f2 L, Avogaro A (2005) Diabetes induces p66shc gene expression in human peripheral blood mononuclear cells: relationship to oxidative stress. J Clin Endocrinol Metab 90:1130\u20131136","journal-title":"J Clin Endocrinol Metab"},{"key":"3563_CR22","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1038\/sj.onc.1205513","volume":"21","author":"M Trinei","year":"2002","unstructured":"Trinei M, Giorgio M, Cicalese A et al (2002) A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene 21:3872\u20133878","journal-title":"Oncogene"},{"key":"3563_CR23","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1161\/CIRCRESAHA.108.181644","volume":"103","author":"CS Kim","year":"2008","unstructured":"Kim CS, Jung SB, Naqvi A et al (2008) P53 impairs endothelium-dependent vasomotor function through transcriptional upregulation of p66Shc. Circ Res 103:1441\u20131450","journal-title":"Circ Res"},{"key":"3563_CR24","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.2337\/db09-1187","volume":"59","author":"SV Kreutzenberg de","year":"2010","unstructured":"de Kreutzenberg SV, Ceolotto G, Papparella I et al (2010) Downregulation of the longevity-associated protein sirtuin 1 in insulin resistance and metabolic syndrome: potential biochemical mechanisms. Diabetes 59:1006\u20131015","journal-title":"Diabetes"},{"key":"3563_CR25","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1038\/nprot.2009.150","volume":"4","author":"DS Li","year":"2009","unstructured":"Li DS, Yuan YH, Tu HJ, Liang QL, Dai LJ (2009) A protocol for islet isolation from mouse pancreas. Nat Protoc 4:1649\u20131652","journal-title":"Nat Protoc"},{"issue":"Suppl 1","key":"3563_CR26","doi-asserted-by":"crossref","first-page":"S134","DOI":"10.2337\/diabetes.51.2007.S134","volume":"51","author":"R Lupi","year":"2002","unstructured":"Lupi R, del Guerra S, Fierabracci V et al (2002) Lipotoxicity in human pancreatic islets and the protective effect of metformin. Diabetes 51(Suppl 1):S134\u2013S137","journal-title":"Diabetes"},{"key":"3563_CR27","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1530\/eje.1.01856","volume":"152","author":"C Santangelo","year":"2005","unstructured":"Santangelo C, Scipioni A, Marselli L, Marchetti P, Dotta F (2005) Suppressor of cytokine signaling gene expression in human pancreatic islets: modulation by cytokines. Eur J Endocrinol 152:485\u2013489","journal-title":"Eur J Endocrinol"},{"key":"3563_CR28","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1210\/en.2009-1166","volume":"151","author":"A Natalicchio","year":"2010","unstructured":"Natalicchio A, de Stefano F, Orlando MR et al (2010) Exendin-4 prevents c-Jun N-terminal protein kinase activation by tumor necrosis factor-alpha (TNFalpha) and inhibits TNFalpha-induced apoptosis in insulin-secreting cells. Endocrinology 151:2019\u20132029","journal-title":"Endocrinology"},{"key":"3563_CR29","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1172\/JCI29103","volume":"116","author":"M Prentki","year":"2006","unstructured":"Prentki M, Nolan CJ (2006) Islet beta cell failure in type 2 diabetes. J Clin Invest 116:1802\u20131812","journal-title":"J Clin Invest"},{"key":"3563_CR30","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1111\/j.1464-5491.2007.02186.x","volume":"24","author":"JP Wilding","year":"2007","unstructured":"Wilding JP (2007) The importance of free fatty acids in the development of type 2 diabetes. Diabet Med 24:934\u2013945","journal-title":"Diabet Med"},{"key":"3563_CR31","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.tiv.2006.02.007","volume":"20","author":"AK Azevedo-Martins","year":"2006","unstructured":"Azevedo-Martins AK, Monteiro AP, Lima CL, Lenzen S, Curi R (2006) Fatty acid-induced toxicity and neutral lipid accumulation in insulin-producing RINm5F cells. Toxicol In Vitro 20:1106\u20131113","journal-title":"Toxicol In Vitro"},{"key":"3563_CR32","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1210\/en.2005-1494","volume":"147","author":"E Karaskov","year":"2006","unstructured":"Karaskov E, Scott C, Zhang L, Teodoro T, Ravazzola M, Volchuk A (2006) Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress, which may contribute to INS-1 pancreatic beta cell apoptosis. Endocrinology 147:3398\u20133407","journal-title":"Endocrinology"},{"key":"3563_CR33","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.metabol.2011.09.005","volume":"61","author":"HJ Wang","year":"2012","unstructured":"Wang HJ, Lee EY, Han SJ et al (2012) Dual pathways of p53 mediated glucolipotoxicity-induced apoptosis of rat cardiomyoblast cell: activation of p53 proapoptosis and inhibition of Nrf2-NQO1 antiapoptosis. Metabolism 61:496\u2013503","journal-title":"Metabolism"},{"key":"3563_CR34","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.jhep.2012.05.013","volume":"57","author":"K Tomita","year":"2012","unstructured":"Tomita K, Teratani T, Suzuki T et al (2012) p53\/p66Shc-mediated signaling contributes to the progression of non-alcoholic steatohepatitis in humans and mice. J Hepatol 57:837\u2013843","journal-title":"J Hepatol"},{"key":"3563_CR35","first-page":"5171","volume":"60","author":"CP Yang","year":"2000","unstructured":"Yang CP, Horwitz SB (2000) Taxol mediates serine phosphorylation of the 66-kDa Shc isoform. Cancer Res 60:5171\u20135178","journal-title":"Cancer Res"},{"key":"3563_CR36","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1083\/jcb.200410041","volume":"169","author":"WW Smith","year":"2005","unstructured":"Smith WW, Norton DD, Gorospe M (2005) Phosphorylation of p66Shc and forkhead proteins mediates Abeta toxicity. J Cell Biol 169:331\u2013339","journal-title":"J Cell Biol"},{"key":"3563_CR37","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1073\/pnas.0336359100","volume":"100","author":"C Napoli","year":"2003","unstructured":"Napoli C, Martin-Padura I, de Nigris F et al (2003) Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet. Proc Natl Acad Sci U S A 100:2112\u20132116","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3563_CR38","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.1091\/mbc.E05-04-0301","volume":"16","author":"Y Hu","year":"2005","unstructured":"Hu Y, Wang X, Zeng L et al (2005) ERK phosphorylates p66ShcA on Ser36 and subsequently regulates p27kip1 expression via the Akt-FoxO3a pathway: implication of p27kip1 in cell response to oxidative stress. Mol Biol Cell 16:3705\u20133718","journal-title":"Mol Biol Cell"},{"key":"3563_CR39","doi-asserted-by":"crossref","first-page":"48332","DOI":"10.1074\/jbc.M106612200","volume":"276","author":"S Le","year":"2001","unstructured":"Le S, Connors TJ, Maroney AC (2001) c-Jun N-terminal kinase specifically phosphorylates p66ShcA at serine 36 in response to ultraviolet irradiation. J Biol Chem 276:48332\u201348336","journal-title":"J Biol Chem"},{"key":"3563_CR40","doi-asserted-by":"crossref","first-page":"26640","DOI":"10.1074\/jbc.M102008200","volume":"276","author":"M Foschi","year":"2001","unstructured":"Foschi M, Franchi F, Han J, La Villa G, Sorokin A (2001) Endothelin-1 induces serine phosphorylation of the adaptor protein p66Shc and its association with 14-3-3 protein in glomerular mesangial cells. J Biol Chem 276:26640\u201326647","journal-title":"J Biol Chem"},{"key":"3563_CR41","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S0167-4889(02)00200-8","volume":"1590","author":"CP Yang","year":"2002","unstructured":"Yang CP, Horwitz SB (2002) Distinct mechanisms of taxol-induced serine phosphorylation of the 66-kDa Shc isoform in A549 and RAW 264.7 cells. Biochim Biophys Acta 1590:76\u201383","journal-title":"Biochim Biophys Acta"},{"key":"3563_CR42","doi-asserted-by":"crossref","first-page":"e81930","DOI":"10.1371\/journal.pone.0081930","volume":"8","author":"L Laviola","year":"2013","unstructured":"Laviola L, Orlando MR, Incalza MA et al (2013) TNF\u03b1 signals via p66(Shc) to induce E-selectin, promote leukocyte transmigration and enhance permeability in human endothelial cells. PLoS One 8:e81930","journal-title":"PLoS One"},{"key":"3563_CR43","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1126\/science.1135380","volume":"315","author":"P Pinton","year":"2007","unstructured":"Pinton P, Rimessi A, Marchi S et al (2007) Protein kinase C beta and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc. Science 315:659\u2013663","journal-title":"Science"},{"key":"3563_CR44","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1210\/me.2010-0189","volume":"24","author":"M Almeida","year":"2010","unstructured":"Almeida M, Han L, Ambrogini E, Bartell SM, Manolagas SC (2010) Oxidative stress stimulates apoptosis and activates NF-\u03baB in osteoblastic cells via a PKC\u03b2\/p66shc signaling cascade: counter regulation by estrogens or androgens. Mol Endocrinol 24:2030\u20132037","journal-title":"Mol Endocrinol"},{"key":"3563_CR45","doi-asserted-by":"crossref","first-page":"F1014","DOI":"10.1152\/ajprenal.00414.2010","volume":"299","author":"L Sun","year":"2010","unstructured":"Sun L, Xiao L, Nie J et al (2010) p66Shc mediates high-glucose and angiotensin II-induced oxidative stress renal tubular injury via mitochondrial-dependent apoptotic pathway. Am J Physiol Ren Physiol 299:F1014\u2013F1025","journal-title":"Am J Physiol Ren Physiol"},{"key":"3563_CR46","doi-asserted-by":"crossref","first-page":"H724","DOI":"10.1152\/ajpheart.00739.2011","volume":"302","author":"J Oshikawa","year":"2012","unstructured":"Oshikawa J, Kim SJ, Furuta E et al (2012) Novel role of p66Shc in ROS-dependent VEGF signaling and angiogenesis in endothelial cells. Am J Physiol Heart Circ Physiol 302:H724\u2013H732","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"3563_CR47","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.cell.2005.05.011","volume":"122","author":"M Giorgio","year":"2005","unstructured":"Giorgio M, Migliaccio E, Orsini F et al (2005) Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 122:221\u2013233","journal-title":"Cell"},{"key":"3563_CR48","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1089\/ars.2006.8.600","volume":"8","author":"E Migliaccio","year":"2006","unstructured":"Migliaccio E, Giorgio M, Pelicci PG (2006) Apoptosis and aging: role of p66Shc redox protein. Antioxid Redox Signal 8:600\u2013608","journal-title":"Antioxid Redox Signal"},{"key":"3563_CR49","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2337\/diabetes.52.1.102","volume":"52","author":"AE Butler","year":"2003","unstructured":"Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta cell deficit and increased beta cell apoptosis in humans with type 2 diabetes. Diabetes 52:102\u2013110","journal-title":"Diabetes"},{"key":"3563_CR50","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1161\/CIRCRESAHA.111.243592","volume":"109","author":"S Zhou","year":"2011","unstructured":"Zhou S, Chen HZ, Wan YZ et al (2011) Repression of p66Shc expression by SIRT1 contributes to the prevention of hyperglycemia-induced endothelial dysfunction. Circ Res 109:639\u2013648","journal-title":"Circ Res"}],"updated-by":[{"DOI":"10.1007\/s00125-015-3739-9","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000}}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-015-3563-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00125-015-3563-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-015-3563-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T08:18:44Z","timestamp":1566461924000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00125-015-3563-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,26]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["3563"],"URL":"https:\/\/doi.org\/10.1007\/s00125-015-3563-2","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,26]]}}}