Laboratory of Diabetes and Obesity, Endocrinology and Nutrition Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic de Barcelona, Villarroel 170, 08036, Barcelona, Spain.
Diabetologia. 2010 Jul;53(7):1406-14. doi: 10.1007/s00125-010-1728-6. Epub 2010 Apr 13.
AIMS/HYPOTHESIS: 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.
CONCLUSIONS/INTERPRETATION: 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.
目的/假设：跨膜蛋白 27（TMEM27）是一种由胰腺β细胞切割和脱落的膜蛋白，被提出作为β细胞质量的生物标志物。尽管有报道称其可能在胰岛素胞吐和细胞增殖中发挥作用，但它在β细胞中的功能仍存在争议。我们旨在研究 TMEM27 在胰岛中的功能及其作为β细胞质量生物标志物的潜在用途。
为了确定 TMEM27 的功能，我们研究了 TMEM27 在人健康和糖尿病胰岛中的基因表达和定位，其表达与人胰岛中细胞周期和胰岛素分泌基因的相关性，在钨酸盐处理的大鼠中的表达，以及其过表达对β细胞系和胰岛中胰岛素分泌和增殖的影响。为了阐明其作为β细胞质量生物标志物的用途，我们研究了β细胞系、胰岛和原代近端肾小管细胞中 TMEM27 的切割。
与对照组相比，糖尿病供体胰岛中的 TMEM27 mRNA 水平较低。其基因表达与人胰岛中的胰岛素和 SNAPIN 相关。钨酸盐处理的大鼠胰岛中的 TMEM27 表达下调，其胰岛素分泌减少，增殖增加。β细胞系和胰岛中 TMEM27 的过表达显著增强了葡萄糖诱导的胰岛素分泌，但对增殖的影响较小或没有。最后，TMEM27 被肾脏近端肾小管细胞和胰腺胰岛切割和脱落。
结论/解释：我们的数据支持 TMEM27 在葡萄糖诱导的胰岛素分泌中的作用，但不是在细胞增殖中的作用。其切割不仅限于β细胞的发现，挑战了当前对其作为潜在β细胞质量生物标志物的支持。
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