Regulating the beta cell mass as a strategy for type-2 diabetes treatment

Current Drug Targets

Volumn 16, Issue 5, 2015, Pages 516-524

  Song, Imane ^a   Muller, Christo ^b   Louw, Johan ^b   Bouwens, Luc ^a  

^a VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

^b SOUTH AFRICAN MEDICAL RESEARCH COUNCIL   (South Africa)

Author keywords

Beta cells; Diabetes; Insulin; Islets; Pancreas; Regenerative medicine

Indexed keywords

CASPASE 3; CILIARY NEUROTROPHIC FACTOR; EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; EXENDIN 4; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON LIKE PEPTIDE 1; HISTONE DEACETYLASE INHIBITOR; INCRETIN; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 1BETA; KERATINOCYTE GROWTH FACTOR; LEUKEMIA INHIBITORY FACTOR; LIOTHYRONINE; PHENYLPYRUVIC ACID; PROTEIN BAD; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; SCATTER FACTOR; SOMATOMEDIN; TRANSCRIPTION FACTOR FKHR; ANTIDIABETIC AGENT;

ARTICLE; CELL DEATH; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SURVIVAL; CHROMATIN IMMUNOPRECIPITATION; DISEASE COURSE; ENDOPLASMIC RETICULUM STRESS; GLUCONEOGENESIS; HIGH THROUGHPUT SCREENING; HUMAN; IMMUNOHISTOCHEMISTRY; INSULIN RELEASE; INSULIN RESISTANCE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; UPREGULATION; ANIMAL; DIABETES MELLITUS, TYPE 2; DRUG EFFECTS; PATHOLOGY; PHYSIOLOGY; REGENERATIVE MEDICINE;

ANIMALS; CELL PROLIFERATION; CELL SURVIVAL; DIABETES MELLITUS, TYPE 2; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN-SECRETING CELLS; REGENERATIVE MEDICINE;

EID: 84929668026     PISSN: 13894501     EISSN: 18735592     Source Type: Journal    
DOI: 10.2174/1389450116666150204113928     Document Type: Article

References (105)

1. [I] Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet 2014; 383(9922): 1068-83.
2. [2] Weir GC, Bonner-Weir S. Islet beta cell mass in diabetes and how it relates to function, birth, and death. Ann NY Acad Sci. 2013;1281: 92-105.
3. [3] Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC. Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab 2008; 10 Suppl 4: 32-42.
4. [4] Yoon KH, Ko SH, Cho JH, et al. Selective beta-cell loss and alpha- cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 2003; 88(5): 2300-8.
5. [5] Butler AE, Janson J, Bonner-Weir S, et al. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003; 52(1): 102-10.
6. [6] Solar M, Cardalda C, Houbracken I, et al. Pancreatic exocrine duct cells give rise to insulin-producing beta cells during embryogenesis but not after birth. Dev Cell 2009; 17(6): 849-60.
7. [7] Dor Y, Brown J, Martinez OI, Melton DA. Adult pancreatic beta- cells are formed by self-duplication rather than stem-cell differentiation. Nature 2004; 429(6987): 41-6.
8. [8] Bernal-Mizrachi E, Kulkarni RN, Scott DK, et al. Human beta-cell proliferation and intracellular signaling part 2: still driving in the dark without a road map. Diabetes 2014; 63(3): 819-31.
9. [9] Kulkarni RN, Mizrachi EB, Ocana AG, Stewart AF. Human beta- cell proliferation and intracellular signaling: driving in the dark without a road map. Diabetes 2012; 61(9): 2205-13.
10. [10] Parnaud G, Bosco D, Berney T, et al. Proliferation of sorted human and rat beta cells. Diabetologia 2008; 51(1): 91-100.
11. 11[] Menge BA, Tannapfel A, Belyaev O, et al. Partial pancreatectomy in adult humans does not provoke beta-cell regeneration. Diabetes 2008; 57(1): 142-9.
12. [12] Alonso LC, Yokoe T, Zhang P, et al. Glucose infusion in mice: a new model to induce beta-cell replication. Diabetes 2007; 56(7): 1792-801.
13. [13] Topp BG, McArthur MD, Finegood DT. Metabolic adaptations to chronic glucose infusion in rats. Diabetologia 2004; 47(9): 1602-10.
14. [14] Tyrberg B, Eizirik DL, Hellerstrom C, Pipeleers DG, Andersson A. Human pancreatic beta-cell deoxyribonucleic acid-synthesis in islet grafts decreases with increasing organ donor age but increases in response to glucose stimulation in vitro. Endocrinology 1996; 137(12): 5694-9.
15. [15] Bonner-Weir S, Deery D, Leahy JL, Weir GC. Compensatory growth of pancreatic beta-cells in adult rats after short-term glucose infusion. Diabetes 1989; 38(1): 49-53.
16. [16] Porat S, Weinberg-Corem N, Tornovsky-Babaey S, et al. Control of pancreatic beta cell regeneration by glucose metabolism. Cell Metab 2011; 13(4): 440-9.
17. [17] Nakamura A, Terauchi Y, Ohyama S, et al. Impact of small-molecule glucokinase activator on glucose metabolism and beta-cell mass. Endocrinology 2009; 150(3): 1147-54.
18. [18] Futamura M, Yao J, Li X, et al. Chronic treatment with a glucokinase activator delays the onset of hyperglycaemia and preserves beta cell mass in the Zucker diabetic fatty rat. Diabetologia 2012; 55(4): 1071-80.
19. [19] Wang W, Walker JR, Wang X, et al. Identification of small-molecule inducers of pancreatic beta-cell expansion. Proc Natl Acad Sci USA 2009; 106(5): 1427-32.
20. [20] Heit JJ, Apelqvist AA, Gu X, et al. Calcineurin/NFAT signalling regulates pancreatic beta-cell growth and function. Nature 2006; 443(7109): 345-9.
21. [21] Andersson O, Adams BA, Yoo D, et al. Adenosine signaling promotes regeneration of pancreatic beta cells in vivo. Cell Metab 2012; 15(6): 885-94.
22. [22] Xu X, D'Hoker J, Stange G, et al. Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 2008; 132(2): 197-207.
23. [23] Annes JP, Ryu JH, Lam K, et al. Adenosine kinase inhibition selectively promotes rodent and porcine islet beta-cell replication. Proc Natl Acad Sci USA 2012; 109(10): 3915-20.
24. [24] Shen W, Tremblay MS, Deshmukh VA, et al. Small-molecule inducer of beta cell proliferation identified by high-throughput screening. J Am Chem Soc 2013; 135(5): 1669-72.
25. [25] Vasavada RC, Gonzalez-Pertusa JA, Fujinaka Y, et al. Growth factors and beta cell replication. Int J Biochem Cell Biol 2006; 38(5-6): 931-50.
26. [26] Bouwens L, Rooman I. Regulation of pancreatic beta-cell mass. Physiol Rev 2005; 85(4): 1255-70.
27. [27] Nielsen JH, Svensson C, Galsgaard ED, Moldrup A, Billestrup N. Beta cell proliferation and growth factors. J Mol Med (Berl) 1999; 77(1): 62-6.
28. [28] Sorenson RL, Brelje TC. Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones. Horm Metab Res 1997; 29(6): 301-7.
29. [29] Xu G, Stoffers DA, Habener JF, Bonner-Weir S. Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes 1999; 48(12): 2270-6.
30. [30] Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007; 132(6): 2131-57.
31. [31] Yabe D, Seino Y. Two incretin hormones GLP-1 and GIP: comparison of their actions in insulin secretion and beta cell preservation. Prog Biophys Mol Biol 2011; 107(2): 248-56.
32. [32] Ding L, Gysemans C, Mathieu C. beta-Cell differentiation and regeneration in type 1 diabetes. Diabetes Obes Metab 2013; 15 Suppl 3: 98-104.
33. [33] Butler AE, Campbell-Thompson M, Gurlo T, et al. Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes 2013; 62(7): 2595-604.
34. [34] Brelje TC, Bhagroo NV, Stout LE, Sorenson RL. Beneficial effects of lipids and prolactin on insulin secretion and beta-cell proliferation: a role for lipids in the adaptation of islets to pregnancy. J Endocrinol 2008; 197(2): 265-76.
35. [35] Zhang H, Zhang J, Pope CF, et al. Gestational diabetes mellitus resulting from impaired beta-cell compensation in the absence of FoxM1, a novel downstream effector of placental lactogen. Diabetes 2010; 59(1): 143-52.
36. [36] Karnik SK, Chen H, McLean GW, et al. Menin controls growth of pancreatic beta-cells in pregnant mice and promotes gestational diabetes mellitus. Science 2007; 318(5851): 806-9.
37. [37] Vasavada RC, Garcia-Ocana A, Zawalich WS, et al. Targeted expression of placental lactogen in the beta cells of transgenic mice results in beta cell proliferation, islet mass augmentation, and hypoglycemia. J Biol Chem 2000; 275(20): 15399-406.
38. [38] Kim H, Toyofuku Y, Lynn FC, et al. Serotonin regulates pancreatic beta cell mass during pregnancy. Nat Med. 2010; 16(7): 804-8.
39. 39[] Vetere A, Choudhary A, Wagner BK. Strategies to increase pancreatic beta cell mass and function. 2013; Available from: http://www.nature.com/nrd/posters/betacelldiabetes.
40. [40] El Ouaamari A, Kawamori D, Dirice E, et al. Liver-derived systemic factors drive beta cell hyperplasia in insulin-resistant states. Cell Rep 2013; 3(2): 401-10.
41. [41] Yi P, Park JS, Melton DA. Betatrophin: a hormone that controls pancreatic beta cell proliferation. Cell 2013; 153(4): 747-58.
42. [42] Fu Z, Berhane F, Fite A, et al. Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity. Sci Rep 2014; 4: 5013.
43. [43] Jiao Y, Le Lay J, Yu M, Naji A, Kaestner KH. Elevated mouse hepatic betatrophin expression does not increase human beta-cell replication in the transplant setting. Diabetes 2014; 63(4): 1283-8.
44. [44] Basta G, Racanicchi L, Mancuso F, et al. Transdifferentiation molecular pathways of neonatal pig pancreatic duct cells into endocrine cell phenotypes. Transplant Proc 2004; 36(9): 2857-63.
45. [45] Minami K, Okuno M, Miyawaki K, et al. Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells. Proc Natl Acad Sci USA 2005; 102(42): 15116-21.
46. [46] Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA. in vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 2008; 455(7213): 627-32.
47. [47] Kushner JA, Weir GC, Bonner-Weir S. Ductal origin hypothesis of pancreatic regeneration under attack. Cell Metab 2010; 11(1): 2-3.
48. [48] Thorel F, Nepote V, Avril I, et al. Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature 2010; 464(7292): 1149-54.
49. [49] Habener JF, Stanojevic V. alpha-cell role in beta-cell generation and regeneration. Islets 2012; 4(3): 188-98.
50. [50] Miettinen PJ, Huotari M, Koivisto T, et al. Impaired migration and delayed differentiation of pancreatic islet cells in mice lacking EGF-receptors. Development 2000; 127(12): 2617-27.
51. [51] Brand SJ, Fuller PJ. Differential gastrin gene expression in rat gastrointestinal tract and pancreas during neonatal development. J Biol Chem 1988; 263(11): 5341-7.
52. [52] Brand SJ, Tagerud S, Lambert P, et al. Pharmacological treatment of chronic diabetes by stimulating pancreatic beta-cell regeneration with systemic co-administration of EGF and gastrin. Pharmacol Toxicol 2002; 91(6): 414-20.
53. [53] Rooman I, Bouwens L. Combined gastrin and epidermal growth factor treatment induces islet regeneration and restores normoglycaemia in C57Bl6/J mice treated with alloxan. Diabetologia 2004; 47(2): 259-65.
54. [54] Suarez-Pinzon WL, Yan Y, Power R, Brand SJ, Rabinovitch A. Combination therapy with epidermal growth factor and gastrin increases beta-cell mass and reverses hyperglycemia in diabetic NOD mice. Diabetes 2005; 54(9): 2596-601.
55. [55] Suarez-Pinzon WL, Lakey JR, Brand SJ, Rabinovitch A. Combination therapy with epidermal growth factor and gastrin induces neogenesis of human islet {beta}-cells from pancreatic duct cells and an increase in functional {beta}-cell mass. J Clin Endocrinol Metab 2005; 90(6): 3401-9.
56. [56] Uzan B, Figeac F, Portha B, Movassat J. Mechanisms of KGF mediated signaling in pancreatic duct cell proliferation and differentiation. PLoS One 2009; 4(3): e4734.
57. [57] Xu G, Kaneto H, Lopez-Avalos MD, Weir GC, Bonner-Weir S. GLP-1/exendin-4 facilitates beta-cell neogenesis in rat and human pancreatic ducts. Diabetes Res Clin Pract 2006; 73(1): 107-10.
58. [58] Bulotta A, Hui H, Anastasi E, et al. Cultured pancreatic ductal cells undergo cell cycle re-distribution and beta-cell-like differentiation in response to glucagon-like peptide-1. J Mol Endocrinol 2002; 29(3): 347-60.
59. [59] Kopinke D, Murtaugh LC. Exocrine-to-endocrine differentiation is detectable only prior to birth in the uninjured mouse pancreas. BMC Dev Biol 2010; 10: 38.
60. [60] Kopp JL, Dubois CL, Schaffer AE, et al. Sox9+ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas. Development 2011; 138(4): 653-65.
61. [61] Furuyama K, Kawaguchi Y, Akiyama H, et al. Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nat Genet 2011; 43(1): 34-41.
62. [62] Baeyens L, Lemper M, Leuckx G, et al. Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice. Nat Biotechnol 2013; 32(1): 76-83.
63. [63] Baeyens L, De Breuck S, Lardon J, et al. In vitro generation of insulin-producing beta cells from adult exocrine pancreatic cells. Diabetologia 2005; 48(1): 49-57.
64. 64[] Baeyens L, Bonne S, Bos T, et al. Notch signaling as gatekeeper of rat acinar-to-beta-cell conversion in vitro. Gastroenterology 2009; 136(5): 1750-60 e13.
65. [65] Herrera PL. Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages. Development 2000; 127(11): 2317-22.
66. [66] Chung CH, Hao E, Piran R, Keinan E, Levine F. Pancreatic beta-cell neogenesis by direct conversion from mature alpha-cells. Stem Cells 2010; 28(9): 1630-8.
67. [67] Bramswig NC, Everett LJ, Schug J, et al. Epigenomic plasticity enables human pancreatic alpha to beta cell reprogramming. J Clin Invest 2013; 123(3): 1275-84.
68. [68] Donath MY, Ehses JA, Maedler K, et al. Mechanisms of beta-cell death in type 2 diabetes. Diabetes 2005; 54 Suppl 2: S108-13.
69. [69] Cunha DA, Igoillo-Esteve M, Gurzov EN, et al. Death protein 5 and p53-upregulated modulator of apoptosis mediate the endoplasmic reticulum stress-mitochondrial dialog triggering lipotoxic rodent and human beta-cell apoptosis. Diabetes 2012; 61(11): 2763-75.
70. [70] Mahadevan J, Parazzoli S, Oseid E, et al. Ebselen treatment prevents islet apoptosis, maintains intranuclear Pdx-1 and MafA levels, and preserves beta-cell mass and function in ZDF rats. Diabetes 2013; 62(10): 3582-8.
71. [71] Gilbert ER, Liu D. Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic beta-cell function. Food Funct 2013; 4(2): 200-12.
72. [72] Babu PV, Liu D, Gilbert ER. Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J Nutr Biochem 2013; 24(11): 1777-89.
73. [73] Szkudelski T, Szkudelska K. Anti-diabetic effects of resveratrol. Ann N Y Acad Sci. 2011; 1215: 34-9.
74. [74] Mathijs I, Da Cunha DA, Himpe E, et al. Phenylpropenoic acid glucoside augments pancreatic beta cell mass in high-fat diet-fed mice and protects beta cells from ER stress-induced apoptosis. Mol Nutr Food Res 2014; 58(10): 1980-90.
75. [75] Wang C, Guan Y, Yang J. Cytokines in the Progression of Pancreatic beta-Cell Dysfunction. Int J Endocrinol 2010; 2010: 515136.
76. [76] Akash MS, Rehman K, Chen S. Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus. J Cell Biochem 2013; 114(3): 525-31.
77. [77] Banerjee M, Saxena M. Interleukin-1 (IL-1) family of cytokines: role in type 2 diabetes. Clin Chim Acta 2012; 413(15-16): 1163-70.
78. [78] Feve B, Bastard JP. The role of interleukins in insulin resistance and type 2 diabetes mellitus. Nat Rev Endocrinol 2009; 5(6): 305-11.
79. [79] Maedler K, Sergeev P, Ris F, et al. Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 2002; 110(6): 851-60.
80. [80] Welsh N, Cnop M, Kharroubi I, et al. Is there a role for locally produced interleukin-1 in the deleterious effects of high glucose or the type 2 diabetes milieu to human pancreatic islets? Diabetes 2005; 54(11): 3238-44.
81. [81] Sandberg JO, Andersson A, Eizirik DL, Sandler S. Interleukin-1 receptor antagonist prevents low dose streptozotocin induced diabetes in mice. Biochem Biophys Res Commun 1994; 202(1): 543-8.
82. [82] Nicoletti F, Di Marco R, Barcellini W, et al. Protection from experimental autoimmune diabetes in the non-obese diabetic mouse with soluble interleukin-1 receptor. Eur J Immunol 1994; 24(8): 1843-7.
83. [83] Thomas HE, Irawaty W, Darwiche R, et al. IL-1 receptor deficiency slows progression to diabetes in the NOD mouse. Diabetes 2004; 53(1): 113-21.
84. [84] Larsen CM, Faulenbach M, Vaag A, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 2007; 356(15): 1517-26.
85. [85] Chen F, Zhou X, Lin Y, et al. Resveratrol prevents interleukin-1beta-induced dysfunction of pancreatic beta-cells. J Biomed Res 2010; 24(5): 381-8.
86. [86] Ku CR, Lee HJ, Kim SK, et al. Resveratrol prevents streptozotocin-induced diabetes by inhibiting the apoptosis of pancreatic beta-cell and the cleavage of poly (ADP-ribose) polymerase. Endocr J 2012; 59(2): 103-9.
87. [87] Lewis EC, Blaabjerg L, Storling J, et al. The oral histone deacetylase inhibitor ITF2357 reduces cytokines and protects islet beta cells in vivo and in vitro. Mol Med 2011; 17(5-6): 369-77.
88. [88] Larsen L, Tonnesen M, Ronn SG, et al. Inhibition of histone deacetylases prevents cytokine-induced toxicity in beta cells. Diabetologia 2007; 50(4): 779-89.
89. [89] Liu XH, Wang YP, Wang LX, et al. Exendin-4 protects murine MIN6 pancreatic beta-cells from interleukin-1beta-induced apoptosis via the NF-kappaB pathway. J Endocrinol Invest 2013; 36(10): 803-11.
90. [90] Ferdaoussi M, Abdelli S, Yang JY, et al. Exendin-4 protects beta-cells from interleukin-1 beta-induced apoptosis by interfering with the c-Jun NH2-terminal kinase pathway. Diabetes 2008; 57(5): 1205-15.
91. [91] Li L, El-Kholy W, Rhodes CJ, Brubaker PL. Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B. Diabetologia 2005; 48(7): 1339-49.
92. [92] Kwon DY, Kim YS, Ahn IS, et al. Exendin-4 potentiates insulinotropic action partly via increasing beta-cell proliferation and neogenesis and decreasing apoptosis in association with the attenuation of endoplasmic reticulum stress in islets of diabetic rats. J Pharmacol Sci 2009; 111(4): 361-71.
93. [93] Shimoda M, Kanda Y, Hamamoto S, et al. The human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes. Diabetologia 2011; 54(5): 1098-108.
94. [94] Farilla L, Bulotta A, Hirshberg B, et al. Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 2003; 144(12): 5149-58.
95. [95] Tiano JP, Mauvais-Jarvis F. Importance of oestrogen receptors to preserve functional beta-cell mass in diabetes. Nat Rev Endocrinol 2012; 8(6): 342-51.
96. [96] Le May C, Chu K, Hu M, et al. Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice. Proc Natl Acad Sci USA 2006; 103(24): 9232-7.
97. [97] Eckhoff DE, Smyth CA, Eckstein C, et al. Suppression of the c-Jun N-terminal kinase pathway by 17beta-estradiol can preserve human islet functional mass from proinflammatory cytokine-induced destruction. Surgery 2003; 134(2): 169-79.
98. [98] Contreras JL, Smyth CA, Bilbao G, et al. 17beta-Estradiol protects isolated human pancreatic islets against proinflammatory cytokine-induced cell death: molecular mechanisms and islet functionality. Transplantation 2002; 74(9): 1252-9.
99. [99] Verga Falzacappa C, Panacchia L, Bucci B, et al. 3,5,3'-triiodothyronine (T3) is a survival factor for pancreatic beta-cells undergoing apoptosis. J Cell Physiol 2006; 206(2): 309-21.
100. [100] Verga Falzacappa C, Mangialardo C, Madaro L, et al. Thyroid hormone T3 counteracts STZ induced diabetes in mouse. PLoS One 2011; 6(5): e19839.
101. [101] Kondegowda NG, Zhang X, Williams K, Mozar A, Vasavada RC. Growth factor mediated regulation of beta cell survival. Open Endocrinol J 2010; 4: 78-93.
102. [102] Jonas JC, Sharma A, Hasenkamp W, et al. Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes. J Biol Chem 1999; 274(20): 14112-21.
103. [103] Talchai C, Xuan S, Lin HV, Sussel L, Accili D. Pancreatic beta cell dedifferentiation as a mechanism of diabetic beta cell failure. Cell 2012; 150(6): 1223-34.
104. [104] Fiori JL, Shin YK, Kim W, et al. Resveratrol prevents beta-cell dedifferentiation in nonhuman primates given a high-fat/high-sugar diet. Diabetes 2013; 62(10): 3500-13.
105. [105] Wang Z, York NW, Nichols CG, Remedi MS. Pancreatic beta cell dedifferentiation in diabetes and redifferentiation following insulin therapy. Cell Metab 2014; 19(5): 872-82.