Bace2 Is a β Cell-Enriched Protease that Regulates Pancreatic β Cell Function and Mass

被引：116

作者：

Esterhazy, Daria ^{[1
,2
]}

Stuetzer, Ina ^{[1
,2
]}

Wang, Haiyan ^{[3
]}

Rechsteiner, Markus P. ^{[2
,4
]}

Beauchamp, Jeremy ^{[3
]}

Doebeli, Heinz ^{[3
]}

Hilpert, Hans ^{[3
]}

Matile, Hugues ^{[3
]}

Prummer, Michael ^{[3
]}

Schmidt, Alexander ^{[1
,2
]}

Lieske, Nora ^{[1
]}

Boehm, Bernhard ^{[6
]}

Marselli, Lorella ^{[7
]}

Bosco, Domenico ^{[10
]}

Kerr-Conte, Julie ^{[11
]}

Aebersold, Ruedi ^{[1
,2
,8
]}

Spinas, Giatgen Andreia ^{[2
,5
]}

Moch, Holger ^{[2
,4
]}

Migliorini, Cristiano ^{[3
]}

Stoffel, Markus ^{[1
,2
,9
]}

机构：

[1] ETH, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland

[2] ETH, Competence Ctr Syst Physiol & Metab Dis, CH-8093 Zurich, Switzerland

[3] F Hoffmann La Roche, CH-4070 Basel, Switzerland

[4] Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland

[5] Univ Zurich Hosp, Div Endocrinol Diabet & Clin Nutr, CH-8091 Zurich, Switzerland

[6] Univ Ulm, Div Endocrinol & Diabet, D-89070 Ulm, Germany

[7] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA

[8] Univ Zurich, Fac Sci, CH-8091 Zurich, Switzerland

[9] Univ Zurich, Fac Med, CH-8091 Zurich, Switzerland

[10] Univ Hosp Geneva, Cell Isolat & Transplantat Ctr, CH-1121 Geneva, Switzerland

[11] Univ Lille 2, INSERM, U859, Dept Surg, F-59045 Lille, France

来源：

CELL METABOLISM | 2011年 / 14卷 / 03期

关键词：

AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; INSULIN-SECRETION; MICE LACKING; ASP1; BACE2; COLLECTRIN; IDENTIFICATION; EXPRESSION; MOUSE; RAT;

D O I：

10.1016/j.cmet.2011.06.018

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Decreased beta cell mass and function are hallmarks of type 2 diabetes. Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human beta cells. Mice with functionally inactive Bace2 and insulin-resistant mice treated with a newly identified Bace2 inhibitor both display augmented beta cell mass and improved control of glucose homeostasis due to increased insulin levels. These results implicate Bace2 in the control of beta cell maintenance and provide a rational strategy to inhibit this protease for the expansion of functional pancreatic beta cell mass.

引用

页码：365 / 377

页数：13

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