Eizirik DL, Mandrup-Poulsen T (2001) A choice of death—the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia 44:2115–2133
Thomas HE, McKenzie MD, Angstetra E et al (2009) Beta cell apoptosis in diabetes. Apoptosis 14:1389–1404
Gurzov EN, Eizirik DL (2011) Bcl-2 proteins in diabetes: mitochondrial pathways of β-cell death and dysfunction. Trends Cell Biol 21:424–431
Herold KC, Vignali DAA, Cooke A, Bluestone JA (2013) Type 1 diabetes: translating mechanistic observations into effective clinical outcomes. Nat Rev Immunol 13:243–256
Schlessinger J, Ullrich A (1992) Growth factor signaling by receptor tyrosine kinases. Neuron 9:383–391
Citri A, Yarden Y (2006) EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 7:505–516
Kritzik MR, Krahl T, Good A et al (2000) Expression of ErbB receptors during pancreatic islet development and regrowth. J Endocrinol 165:67–77
Huotari M-A, Miettinen PJ, Palgi J et al (2002) ErbB signaling regulates lineage determination of developing pancreatic islet cells in embryonic organ culture. Endocrinology 143:4437–4446
Miettinen PJ, Huotari M, Koivisto T et al (2000) Impaired migration and delayed differentiation of pancreatic islet cells in mice lacking EGF-receptors. Development 127:2617–2627
Miettinen PJ, Ustinov J, Ormio P et al (2006) Downregulation of EGF receptor signaling in pancreatic islets causes diabetes due to impaired postnatal beta-cell growth. Diabetes 55:3299–3308
Cras-Meneur C, Elghazi L, Czernichow P, Scharfmann R (2001) Epidermal growth factor increases undifferentiated pancreatic embryonic cells in vitro: a balance between proliferation and differentiation. Diabetes 50:1571–1579
Miettinen P, Ormio P, Hakonen E et al (2008) EGF receptor in pancreatic beta-cell mass regulation. Biochem Soc Trans 36:280–285
Elghazi L, Bernal-Mizrachi E (2009) Akt and PTEN: beta-cell mass and pancreas plasticity. Trends Endocrinol Metab 20:243–251
Choi SH, Mendrola JM, Lemmon MA (2007) EGF-independent activation of cell-surface EGF receptors harboring mutations found in gefitinib-sensitive lung cancer. Oncogene 26:1567–1576
Shan Y, Eastwood MP, Zhang X et al (2012) Oncogenic mutations counteract intrinsic disorder in the EGFR kinase and promote receptor dimerization. Cell 149:860–870
Nir T, Melton D, Dor Y (2007) Recovery from diabetes in mice by beta cell regeneration. J Clin Invest 117:2553–2561
Politi K, Zakowski MF, Fan P-D, Schonfeld EA, Pao W, Varmus HE (2006) Lung adenocarcinomas induced in mice by mutant EGF receptors found in human lung cancers respond to a tyrosine kinase inhibitor or to down-regulation of the receptors. Genes Dev 20:1496–1510
Hakonen E, Ustinov J, Mathijs I et al (2011) Epidermal growth factor (EGF)-receptor signalling is needed for murine beta cell mass expansion in response to high-fat diet and pregnancy but not after pancreatic duct ligation. Diabetologia 54:1735–1743
Alanentalo T, Asayesh A, Morrison H et al (2007) Tomographic molecular imaging and 3D quantification within adult mouse organs. Nat Methods 4:31–33
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408
Liu D, Pavlovic D, Chen MC, Flodström M, Sandler S, Eizirik DL (2000) Cytokines induce apoptosis in beta-cells isolated from mice lacking the inducible isoform of nitric oxide synthase (iNOS−/−). Diabetes 49:1116–1122
Flodström M, Tyrberg B, Eizirik DL, Sandler S (1999) Reduced sensitivity of inducible nitric oxide synthase-deficient mice to multiple low-dose streptozotocin-induced diabetes. Diabetes 48:706–713
Wicksteed B, Brissova M, Yan W et al (2010) Conditional gene targeting in mouse pancreatic ß-cells: analysis of ectopic Cre transgene expression in the brain. Diabetes 59:3090–3098
Irmer D, Funk JO, Blaukat A (2007) EGFR kinase domain mutations—functional impact and relevance for lung cancer therapy. Oncogene 26:5693–5701
Lenzen S (2008) The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 51:216–226
Like AA, Rossini AA (1976) Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science 193:415–417
Eizirik DL, Colli ML, Ortis F (2009) The role of inflammation in insulitis and beta-cell loss in type 1 diabetes. Nat Rev Endocrinol 5:219–226
Sandberg JO, Andersson A, Eizirik DL, Sandler S (1994) Interleukin-1 receptor antagonist prevents low dose streptozotocin induced diabetes in mice. Biochem Biophys Res Commun 202:543–548
Moore F, Naamane N, Colli ML et al (2011) STAT1 is a master regulator of pancreatic β-cell apoptosis and islet inflammation. J Biol Chem 286:929–941
Wang H, Gambosova K, Cooper ZA et al (2010) EGF regulates survivin stability through the Raf-1/ERK pathway in insulin-secreting pancreatic β-cells. BMC Mol Biol 11:66
Teta M, Long S, Wartschow L, Rankin M, Kushner J (2005) Very slow turnover of beta-cells in aged adult mice. Diabetes 54:2557–2567
Meier JJ, Butler AE, Saisho Y et al (2008) Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans. Diabetes 57:1584–1594
Zeng N, Yang K-T, Bayan J-A et al (2013) PTEN controls β-cell regeneration in aged mice by regulating cell cycle inhibitor p16(ink4a.). Aging Cell 12:1000–1011
Bernal-Mizrachi E, Wen W, Stahlhut S, Welling CM, Permutt MA (2001) Islet beta cell expression of constitutively active Akt1/PKB alpha induces striking hypertrophy, hyperplasia, and hyperinsulinemia. J Clin Invest 108:1631–1638
Tuttle RL, Gill NS, Pugh W et al (2001) Regulation of pancreatic beta-cell growth and survival by the serine/threonine protein kinase Akt1/PKBalpha. Nat Med 7:1133–1137
Elghazi L, Weiss AJ, Barker DJ et al (2009) Regulation of pancreas plasticity and malignant transformation by Akt signaling. Gastroenterology 136:1091–1103
Ji H, Li D, Chen L et al (2006) The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell 9:485–495
Sordella R, Bell DW, Haber DA, Settleman J (2004) Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 305:1163–1167
Oh YS, Shin S, Lee Y-J, Kim EH, Jun H-S (2011) Betacellulin-induced beta cell proliferation and regeneration is mediated by activation of ErbB-1 and ErbB-2 receptors. PLoS ONE 6:e23894
Yamamoto H, Uchigata Y, Okamoto H (1981) Streptozotocin and alloxan induce DNA strand breaks and poly(ADP-ribose) synthetase in pancreatic islets. Nature 294:284–286
Kantwerk-Funke G, Burkart V, Kolb H (1991) Low dose streptozotocin causes stimulation of the immune system and of anti-islet cytotoxicity in mice. Clin Exp Immunol 86:266–270
Cnop M, Welsh N, Jonas J-C, Jörns A, Lenzen S, Eizirik DL (2005) Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes 54(Suppl 2):S97–S107
Barthson J, Germano CM, Moore F et al (2011) Cytokines tumor necrosis factor-α and interferon-γ induce pancreatic β-cell apoptosis through STAT1-mediated Bim protein activation. J Biol Chem 286:39632–39643
Santin I, Moore F, Colli ML et al (2011) PTPN2, a candidate gene for type 1 diabetes, modulates pancreatic β-cell apoptosis via regulation of the BH3-only protein Bim. Diabetes 60:3279–3288
Nogueira TC, Paula FM, Villate O et al (2013) GLIS3, a susceptibility gene for type 1 and type 2 diabetes, modulates pancreatic beta cell apoptosis via regulation of a splice variant of the BH3-only protein Bim. PLoS Genet 9:e1003532
Ley R, Ewings KE, Hadfield K, Cook SJ (2005) Regulatory phosphorylation of Bim: sorting out the ERK from the JNK. Cell Death Differ 12:1008–1014
Qi X-J, Wildey GM, Howe PH (2006) Evidence that Ser87 of BimEL is phosphorylated by Akt and regulates BimEL apoptotic function. J Biol Chem 281:813–823
Dijkers PF, Medema RH, Lammers JW, Koenderman L, Coffer PJ (2000) Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1. Curr Biol 10:1201–1204
Gong Y, Somwar R, Politi K et al (2007) Induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomas. PLoS Med 4:e294
Costa DB, Halmos B, Kumar A et al (2007) BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med 4:1669–1679