title: Islet cell plasticity and regeneration.
abstract: Insulin-dependent diabetes is a complex multifactorial disorder characterized by loss or dysfunction of β-cells resulting in failure of metabolic control. Even though type 1 and 2 diabetes differ in their pathogenesis, restoring β-cell function is the overarching goal for improved therapy of both diseases. This could be achieved either by cell-replacement therapy or by triggering intrinsic regenerative mechanisms of the pancreas. For type 1 diabetes, a combination of β-cell replacement and immunosuppressive therapy could be a curative treatment, whereas for type 2 diabetes enhancing endogenous mechanisms of β-cell regeneration might optimize blood glucose control. This review will briefly summarize recent efforts to allow β-cell regeneration where the most promising approaches are currently (1) increasing β-cell self-replication or neogenesis from ductal progenitors and (2) conversion of α-cells into β-cells.
authors.affiliation: Institute of Stem Cell Research, Helmholtz Zentrum München, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany ; Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Am Parkring 11, D-85748, Business Campus Garching, Germany.
authors.forename: Adriana
authors.initials: A
authors.lastname: Migliorini
authors.affiliation: Institute of Stem Cell Research, Helmholtz Zentrum München, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany ; Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Am Parkring 11, D-85748, Business Campus Garching, Germany ; Research Unit of Molecular Epidemiology Institute of Epidemiology II, Helmholtz Zentrum München, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Bader
authors.affiliation: Institute of Stem Cell Research, Helmholtz Zentrum München, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany ; Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Am Parkring 11, D-85748, Business Campus Garching, Germany ; German Center for Diabetes Research (DZD), Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Lickert
keywords: Diabetes; Islet architecture; Pancreas plasticity; β-cell neogenesis; β-cell proliferation; β-cell regeneration
references.citation: Cell Metab. 2013 Jul 2;18(1):5-6
references.pmid: 23823472
references.citation: Islets. 2009 Sep-Oct;1(2):129-36
references.pmid: 20606719
references.citation: Nat Rev Drug Discov. 2013 Jul;12(7):504
references.pmid: 23787955
references.citation: Am J Physiol Endocrinol Metab. 2013 Nov 15;305(10):E1309-18
references.pmid: 24064341
references.citation: Nat Rev Endocrinol. 2013 Jul;9(7):379
references.pmid: 23648871
references.citation: Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16109-14
references.pmid: 24043787
references.citation: Horm Metab Res. 1997 Jun;29(6):301-7
references.pmid: 9230352
references.citation: Nature. 2010 Apr 22;464(7292):1149-54
references.pmid: 20364121
references.citation: Dev Cell. 2009 Dec;17(6):849-60
references.pmid: 20059954
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19915-9
references.pmid: 19052237
references.citation: Mol Endocrinol. 2009 Oct;23(10):1702-12
references.pmid: 19574445
references.citation: Nature. 1997 Mar 27;386(6623):399-402
references.pmid: 9121556
references.citation: J Endocrinol. 2013 Jan 02;216(1):T37-45
references.pmid: 22991412
references.citation: Diabetes. 2010 Oct;59(10):2340-8
references.pmid: 20876724
references.citation: Dev Cell. 2013 Jul 15;26(1):3-7
references.pmid: 23867225
references.citation: Trends Endocrinol Metab. 2010 Mar;21(3):151-8
references.pmid: 20015659
references.citation: Science. 2001 Oct 19;294(5542):564-7
references.pmid: 11577200
references.citation: Drugs. 2013 Mar;73(4):383-91
references.pmid: 23558600
references.citation: PLoS Genet. 2013;9(1):e1003274
references.pmid: 23382704
references.citation: Int J Biochem Cell Biol. 2006;38(5-6):931-50
references.pmid: 16168703
references.citation: Cell Rep. 2013 Feb 21;3(2):401-10
references.pmid: 23375376
references.citation: Diabetes. 1999 Dec;48(12):2270-6
references.pmid: 10580413
references.citation: J Clin Endocrinol Metab. 2013 May;98(5):2053-61
references.pmid: 23539729
references.citation: Cell Metab. 2009 Oct;10(4):285-95
references.pmid: 19808021
references.citation: Dev Cell. 2010 Mar 16;18(3):342-56
references.pmid: 20230744
references.citation: Diabetes. 2008 Apr;57(4):958-66
references.pmid: 18083786
references.citation: Cell. 2013 May 9;153(4):747-58
references.pmid: 23623304
references.citation: J Biol Chem. 2011 Mar 25;286(12):10449-56
references.pmid: 21278380
references.citation: Cell Stem Cell. 2011 Mar 4;8(3):281-93
references.pmid: 21362568
references.citation: Diabetes. 2002 Apr;51(4):1247-55
references.pmid: 11916952
references.citation: Dev Cell. 2006 Mar;10(3):397-405
references.pmid: 16516842
references.citation: Diabetes. 2013 May;62(5):1634-45
references.pmid: 23349489
references.citation: Diabetes. 2001 Mar;50(3):521-33
references.pmid: 11246871
references.citation: Diabetes. 1955 Sep-Oct;4(5):367-76
references.pmid: 13270659
references.citation: Genes Dev. 2003 Oct 15;17(20):2591-603
references.pmid: 14561778
references.citation: Development. 2013 Jun;140(12):2472-83
references.pmid: 23715541
references.citation: J Clin Invest. 2007 Apr;117(4):961-70
references.pmid: 17404619
references.citation: Diabetes. 2007 Apr;56(4):1078-86
references.pmid: 17395748
references.citation: Cell. 2008 Jan 25;132(2):197-207
references.pmid: 18243096
references.citation: Diabetologia. 2014 Jan;57(1):50-3
references.pmid: 24078058
references.citation: Cell Metab. 2009 Oct;10(4):296-308
references.pmid: 19808022
references.citation: J Clin Invest. 2007 Sep;117(9):2553-61
references.pmid: 17786244
references.citation: Cell Metab. 2013 Jul 2;18(1):9-20
references.pmid: 23823474
references.citation: Mol Ther. 2008 May;16(5):854-61
references.pmid: 18388935
references.citation: Dev Cell. 2013 Jul 15;26(1):86-100
references.pmid: 23810513
references.citation: Diabetes. 2003 Sep;52(9):2304-14
references.pmid: 12941770
references.citation: Diabetes Obes Metab. 2008 Nov;10 Suppl 4:32-42
references.pmid: 18834431
references.citation: Dev Cell. 2007 May;12(5):779-92
references.pmid: 17488628
references.citation: Cell. 2012 Sep 14;150(6):1223-34
references.pmid: 22980982
references.citation: Science. 2005 Jan 21;307(5708):380-4
references.pmid: 15662003
references.citation: Mol Cell Endocrinol. 2009 Jan 15;297(1-2):18-27
references.pmid: 18824066
references.citation: J Clin Invest. 2013 May;123(5):2207-17
references.pmid: 23619362
references.citation: Cell Metab. 2006 Mar;3(3):148-50
references.pmid: 16517401
references.citation: Dev Dyn. 2011 Mar;240(3):530-65
references.pmid: 21337462
references.citation: Nat Biotechnol. 2014 Jan;32(1):76-83
references.pmid: 24240391
references.citation: J Clin Invest. 2013 Mar;123(3):990-5
references.pmid: 23454762
references.citation: Endocrinology. 2002 Nov;143(11):4397-408
references.pmid: 12399437
references.citation: Islets. 2010 May-Jun;2(3):135-45
references.pmid: 20657742
references.citation: PLoS One. 2011;6(8):e23894
references.pmid: 21897861
references.citation: Nat Biotechnol. 2004 Sep;22(9):1115-24
references.pmid: 15322557
references.citation: Diabetes. 1988 May;37(5):616-21
references.pmid: 3282948
references.citation: Cytokine Growth Factor Rev. 2013 Feb;24(1):59-68
references.pmid: 22884427
references.citation: J Histochem Cytochem. 2005 Sep;53(9):1087-97
references.pmid: 15923354
references.citation: Dev Cell. 2007 May;12(5):817-26
references.pmid: 17488631
references.citation: Diabetes Obes Metab. 2012 Oct;14 Suppl 3:78-84
references.pmid: 22928567
references.citation: Diabetes Obes Metab. 2013 Jan;15(1):15-27
references.pmid: 22776039
references.citation: Diabetes Obes Metab. 2009 Nov;11 Suppl 4:159-67
references.pmid: 19817798
references.citation: N Engl J Med. 2000 Jul 27;343(4):230-8
references.pmid: 10911004
references.citation: J Mol Biol. 2008 Jun 27;380(1):83-94
references.pmid: 18508082
references.citation: Curr Biol. 2003 Nov 11;13(22):2004-8
references.pmid: 14614828
references.citation: Cell. 2009 Aug 7;138(3):449-62
references.pmid: 19665969
references.citation: Nat Med. 2010 Jul;16(7):804-8
references.pmid: 20581837
references.citation: Cell Metab. 2010 Jan;11(1):2-3
references.pmid: 20085728
references.citation: Diabetologia. 2002 Sep;45(9):1263-73
references.pmid: 12242459
references.citation: Cell Rep. 2012 Dec 27;2(6):1593-606
references.pmid: 23177622
references.citation: Curr Diab Rep. 2012 Oct;12(5):481-9
references.pmid: 22782495
references.citation: IDrugs. 2009 Aug;12(8):503-13
references.pmid: 19629885
references.citation: Nature. 2008 Oct 2;455(7213):627-32
references.pmid: 18754011
references.citation: Nature. 1997 May 22;387(6631):406-9
references.pmid: 9163426
references.citation: Nature. 2004 May 6;429(6987):41-6
references.pmid: 15129273
references.citation: J Clin Invest. 2013 Mar;123(3):1275-84
references.pmid: 23434589
references.citation: Mech Dev. 2006 Jul;123(7):501-12
references.pmid: 16822656
references.citation: Dis Model Mech. 2013 Sep;6(5):1236-45
references.pmid: 23828045
references.citation: Expert Opin Investig Drugs. 2012 Jan;21(1):45-57
references.pmid: 22111970
references.citation: J Biol Chem. 2003 Jan 3;278(1):471-8
references.pmid: 12409292
references.citation: Int J Endocrinol. 2010;2010:515136
references.pmid: 21113299
references.citation: Diabetes. 2010 Dec;59(12):3108-16
references.pmid: 20841608
references.citation: Mol Cell Biol. 2008 Apr;28(7):2414-25
references.pmid: 18227155
references.citation: Diabetes. 2014 Apr;63(4):1283-8
references.pmid: 24353178
references.citation: Prog Biophys Mol Biol. 2011 Nov;107(2):248-56
references.pmid: 21820006
references.citation: Trends Endocrinol Metab. 2010 Aug;21(8):457-63
references.pmid: 20359908
references.citation: Development. 2013 Feb;140(4):751-64
references.pmid: 23325761
references.citation: Diabetologia. 1998 Jun;41(6):629-33
references.pmid: 9662042
references.citation: Diabetes. 2003 Jan;52(1):102-10
references.pmid: 12502499
references.citation: Cell Death Differ. 2008 Jan;15(1):94-104
references.pmid: 17932502
references.citation: Front Endocrinol (Lausanne). 2013 Oct 14;4:146
references.pmid: 24133484