TOSO promotes β-cell proliferation and protects from apoptosis

被引：4

作者：

Dharmadhikari, G. ^{[1
]}

Muehle, M. ^{[2
]}

Schulthess, F. T. ^{[1
,2
]}

Laue, S. ^{[1
]}

Oberholzer, J. ^{[3
]}

Pattou, F. ^{[4
]}

Kerr-Conte, J. ^{[4
]}

Maedler, K. ^{[1
]}

机构：

[1] Univ Bremen, Ctr Biomol Interact Bremen, Leobener Str NW2,Room B2080, D-28359 Bremen, Germany

[2] Univ Calif Los Angeles, Larry Hilolom Islet Res Ctr, Los Angeles, CA USA

[3] Univ Illinois, Div Transplantat, Chicago, IL USA

[4] Univ Lille Nord France, INSERM, Therapie Cellulaire Diabet, Lille, France

来源：

MOLECULAR METABOLISM | 2012年 / 1卷 / 1-2期

基金：

欧洲研究理事会;

关键词：

TOSO; Fas; Islets; beta-cell proliferation; Diabetes; LIGAND-INDUCED APOPTOSIS; FAS LIGAND; PANCREATIC-ISLETS; B-CELLS; DEATH; RECEPTOR; EXPRESSION; MOUSE; INTERLEUKIN-1-BETA; TURNOVER;

D O I：

10.1016/j.molmet.2012.08.006

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Decreased beta-cell mass reflects a shift from quiescence/proliferation into apoptosis, it plays a crucial role in the pathophysiology of diabetes. A major attempt to restore beta-cell mass and normoglycemia is to improve beta-cell survival. Here we show that switching off the Fas pathway using Fas apoptotic inhibitory protein (Faim/TOSO), which regulates apoptosis upstream of caspase 8, blocked (beta-cell apoptosis and increased proliferation in human islets. TOSO was clearly expressed in pancreatic beta-cells and down-regulated in T2DM. TOSO expression correlated with beta-cell turnover; at conditions of improved survival, TOSO was induced. In contrast, TOSO downregulation induced beta-cell apoptosis. Although TOSO overexpression resulted in a 3-fold induction of proliferation, proliferating 13 -cells showed a very limited capacity to undergo multiple rounds of replication. Our data suggest that TOSO is an important regulator of beta-cell turnover and switches beta-cell apoptosis into proliferation. 2012 Elsevier GmbH. Open access under CC-BY-NC-ND license.

引用

页码：70 / 78

页数：9

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