title: Characterization of β-cell plasticity mechanisms induced in mice by a transient source of exogenous insulin.
abstract: β-Cell plasticity governs the adjustment of β-cell mass and function to ensure normoglycemia. The study of how β-cell mass is controlled and the identification of alternative sources of β-cells are active fields of research. β-Cell plasticity has been implicated in numerous physiological and pathological conditions. We developed a mice model in which we induced major β-cell mass atrophy by implanting insulin pellets (IPI) for 7 or 10 days. The implants were then removed (IPR) to observe the timing and characteristics of β-cell regeneration in parallel to changes in glycemia. Following IPR, the endocrine mass was reduced by 60% at day 7 and by 75% at day 10, and transient hyperglycemia was observed, which resolved within 1 wk. Five days after IPR, enhanced β-cell proliferation and an increased frequency of small islets were observed in 7-day IPI mice. β-Cell mass was fully restored after an additional 2 days. For the 10-day IPI group, β-cell and endocrine mass were no longer significantly different from those of the control group at 2 wk post-IPR. Furthermore, real-time quantitative PCR analysis of endocrine structures isolated by laser capture microdissection indicated sequentially enhanced expression of the pancreatic transcription factors β(2)/NeuroD and Pdx-1 post-IPR. Thus, our data suggest this mouse model of β-cell plasticity not only relies on replication but also involves enhanced cell differentiation plasticity.
authors: Service d’Anatomie Pathologique, CHU Mont-Godinne, Institut de recherche expérimentale et clinique, Université catholique de Louvain, Yvoir, Brussels, Belgium. marie-cecile.nollevaux@uclouvain.be
authors: M-C
authors: MC
authors: Nollevaux
authors: J
authors: J
authors: Rahier
authors: J
authors: J
authors: Marchandise
authors: P
authors: P
authors: Thurion
authors: S
authors: S
authors: Godecharles
authors: G
authors: G
authors: Van den Steen
authors: J
authors: J
authors: Jamart
authors: C
authors: C
authors: Sempoux
authors: P
authors: P
authors: Jacquemin
authors: Y
authors: Y
authors: Guiot
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D049108:Cell Enlargement / Q000187:drug effects; D049109:Cell Proliferation; D044903:Congenital Hyperinsulinism; D005260:Female; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D061346:Laser Capture Microdissection; D051379:Mice; D046768:Nesidioblastosis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051273:Glucose Transporter Type 2; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; C495682:Slc2a2 protein, mouse; D014157:Transcription Factors; D005947:Glucose
references: J Clin Endocrinol Metab. 1983 Mar;56(3):441-4
references: 6337179
references: Science. 2007 Nov 2;318(5851):806-9
references: 17975067
references: J Clin Invest. 1983 Jun;71(6):1544-53
references: 6134752
references: Semin Pediatr Surg. 2011 Feb;20(1):3-12
references: 21185997
references: Cell. 2008 Jan 25;132(2):197-207
references: 18243096
references: J Pediatr Surg. 2002 Feb;37(2):155-8
references: 11819190
references: Endocrinology. 2001 Nov;142(11):4956-68
references: 11606464
references: Diabetes Obes Metab. 2008 Nov;10 Suppl 4:32-42
references: 18834431
references: Methods Mol Biol. 2009;560:87-98
references: 19504246
references: Diabetes Obes Metab. 2008 Nov;10 Suppl 4:63-76
references: 18834434
references: Cell. 2008 Jan 25;132(2):183-4
references: 18243094
references: Diabetes. 2003 Mar;52(3):784-94
references: 12606521
references: Diabetologia. 2007 Sep;50(9):1889-1899
references: 17593344
references: J Clin Endocrinol Metab. 2011 Dec;96(12):3785-93
references: 21956412
references: Proc Natl Acad Sci U S A. 1977 Feb;74(2):628-32
references: 191819
references: J Clin Endocrinol Metab. 1998 May;83(5):1455-61
references: 9589638
references: Diabetes. 1989 Jan;38(1):49-53
references: 2642434
references: Diabetes. 2008 Aug;57(8):2137-48
references: 18469203
references: Endocrinology. 1995 Dec;136(12):5461-8
references: 7588296
references: Nature. 2010 Apr 22;464(7292):1149-54
references: 20364121
references: Horm Metab Res. 1997 Jun;29(6):301-7
references: 9230352
references: Br J Cancer. 1986 Oct;54(4):685-92
references: 2877684
references: Endocrinology. 2003 Jun;144(6):2717-27
references: 12746336
references: Diabetologia. 2010 Oct;53(10):2167-76
references: 20523966
references: Dev Cell. 2010 Mar 16;18(3):342-56
references: 20230744
references: Diabetes Obes Metab. 2008 Nov;10 Suppl 4:128-35
references: 18834440
references: Physiol Rev. 2005 Oct;85(4):1255-70
references: 16183912
references: J Clin Endocrinol Metab. 2003 May;88(5):2300-8
references: 12727989
references: J Clin Invest. 1989 Aug;84(2):711-4
references: 2760207
references: Diabetologia. 2008 Feb;51(2):216-26
references: 18087688
references: Cell Metab. 2010 Apr 7;11(4):298-310
references: 20374962
references: J Clin Invest. 2003 Apr;111(8):1147-60
references: 12697734
references: Eur J Pharmacol. 1994 Aug 11;261(1-2):157-61
references: 8001638
references: Diabetes Obes Metab. 2008 Nov;10 Suppl 4:1-4
references: 18834427
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: Diabetologia. 2003 Jan;46(1):3-19
references: 12637977
references: Nature. 2004 May 6;429(6987):41-6
references: 15129273
references: J Cell Sci. 2010 Aug 15;123(Pt 16):2792-802
references: 20663919
references: Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9715-20
references: 19487660
references: Diabetes. 1995 Sep;44(9):1121-5
references: 7657038
references: Diabetes. 2001 Feb;50 Suppl 1:S182-3
references: 11272187
references: Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9559-63
references: 7937805
references: Surv Synth Pathol Res. 1985;4(2):110-25
references: 3901180
references: Diabetes. 2003 Jan;52(1):102-10
references: 12502499
references: J Mol Endocrinol. 2000 Jun;24(3):297-302
references: 10828822