The role of transmembrane protein 27 (TMEM27) in islet physiology and its potential use as a beta cell mass biomarker

被引:28
作者
Altirriba, J. [1 ]
Gasa, R. [1 ]
Casas, S. [1 ]
Ramirez-Bajo, M. J. [2 ]
Ros, S. [3 ]
Gutierrez-Dalmau, A. [2 ,4 ]
Ruiz de Villa, M. C. [5 ]
Barbera, A. [1 ]
Gomis, R. [1 ,6 ]
机构
[1] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, Endocrinol & Nutr Unit, Lab Diabet & Obes, E-08036 Barcelona, Spain
[2] Hosp Clin Barcelona, Lab Expt Nefrol & Trasplantament, Dept Nephrol & Renal Tranplantat, Barcelona, Spain
[3] Inst Res Biomed, Barcelona, Spain
[4] Hosp Univ Miguel Servet, Dept Nephrol, Zaragoza, Spain
[5] Univ Barcelona, Dept Stat, Barcelona, Spain
[6] Univ Barcelona, Dept Med, Barcelona, Spain
关键词
Beta cell; Islet; Biomarker; Insulin secretion; Proliferation; TMEM27; PANCREATIC-ISLETS; COLLECTRIN; TARGET; MICE; PROLIFERATION; REGENERATION; RETENTION;
D O I
10.1007/s00125-010-1728-6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Transmembrane protein 27 (TMEM27) is a membrane protein cleaved and shed by pancreatic beta cells that has been proposed as a beta cell mass biomarker. Despite reports of its possible role in insulin exocytosis and cell proliferation, its function in beta cells remains controversial. We aimed to characterise the function of TMEM27 in islets and its potential use as a beta cell mass biomarker. To determine TMEM27 function, we studied TMEM27 gene expression and localisation in human healthy and diabetic islets, the correlation of its expression with cell cycle and insulin secretion genes in human islets, its expression in tungstate-treated rats, and the effects of its overproduction on insulin secretion and proliferation in a beta cell line and islets. To elucidate its utility as a beta cell mass biomarker, we studied TMEM27 cleavage in a beta cell line, islets and primary proximal tubular cells. TMEM27 mRNA levels in islets are lower in diabetic donors than in controls. Its gene expression correlates with that of insulin and SNAPIN in human islets. TMEM27 expression is downregulated in islets of tungstate-treated rats, which exhibit decreased insulin secretion and increased proliferation. TMEM27 overproduction in a beta cell line and islets significantly enhanced glucose-induced insulin secretion, with modest or no effects on proliferation. Finally, TMEM27 is cleaved and shed by renal proximal tubular cells and pancreatic islets. Our data support a role for TMEM27 in glucose-induced insulin secretion but not in cell proliferation. The finding that its cleavage is not specific to beta cells challenges the current support for its use as a potential beta cell mass biomarker.
引用
收藏
页码:1406 / 1414
页数:9
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