Angiopoietin-like protein 8 (ANGPTL8)/betatrophin overexpression does not increase beta cell proliferation in mice.
Angiopoietin-like protein 8 (ANGPTL8)/betatrophin overexpression does not increase beta cell proliferation in mice.
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DOI：
10.1007/s00125-015-3590-z
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发表时间：
2015-07
期刊：
影响因子：
8.2
通讯作者：
Kushner, Jake A.
中科院分区：
文献类型：
--
作者：
Cox, Aaron R.;Lam, Carol J.;Bonnyman, Claire W.;Chavez, Julia;Rios, Jacqueline S.;Kushner, Jake A.
发现刺激内源性β细胞再生的新靶点将代表糖尿病患者治疗的重大进展。betatrophin假说表明，血管生成素样蛋白8 （ANGPTL8）的表达增加可诱导显著的特异性β细胞增殖和随后的β细胞质量扩增，同时改善葡萄糖耐量。鉴于最近的争议，我们进一步研究了ANGPTL8过表达对β细胞增殖的影响。我们在多个不同年龄的小鼠队列中进行了绿色荧光蛋白（GFP）或Angptl8（也称为Gm6484） DNA的水动力尾静脉注射。我们采用最先进的方法全面量化β细胞质量和增殖，控制小鼠年龄，遗传品系，注射DNA来源，Angptl8基因表达和增殖标志物。在两个年轻和两个老年B6.129小鼠队列中，ANGPTL8过表达后β细胞复制、质量或葡萄糖稳态均未发生实质性变化。即使在Angptl8表达极度升高（增加26倍）的小鼠中，β细胞复制也没有明显改变。最后，我们考虑了与Melton等研究完全相同的ICR背景下的小鼠，ANGPTL8过表达后仍未检测到β细胞有丝分裂作用。ANGPTL8不刺激年轻或年老小鼠的β细胞复制。本文的在线版本（doi:10.1007/s00125-015-3590-z）包含同行评审但未经编辑的补充材料，授权用户可使用。
The identification of novel targets that stimulate endogenous regeneration of beta cells would represent a significant advance in the treatment of patients with diabetes. The betatrophin hypothesis suggests that increased expression of angiopoietin-like protein 8 (ANGPTL8) induces dramatic and specific beta cell proliferation and subsequent beta cell mass expansion with improved glucose tolerance. In light of recent controversy, we further investigated the effects of ANGPTL8 overexpression on beta cell proliferation. We performed hydrodynamic tail vein injections of green fluorescent protein (GFP) or Angptl8 (also known as Gm6484) DNA in multiple cohorts of mice of different ages. We employed state-of-the-art methods to comprehensively quantify beta cell mass and proliferation, controlling for mouse age, genetic strain, source of DNA injected, Angptl8 gene expression and proliferation markers. In two young and two aged cohorts of B6.129 mice, no substantial change in beta cell replication, mass or glucose homeostasis was observed following ANGPTL8 overexpression. Even in mice with extremely elevated Angptl8 expression (26-fold increase), beta cell replication was not significantly altered. Finally, we considered mice on the ICR background exactly as studied by Melton and colleagues, and still no beta cell mitogenic effect was detected following ANGPTL8 overexpression. ANGPTL8 does not stimulate beta cell replication in young or old mice. The online version of this article (doi:10.1007/s00125-015-3590-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
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影响因子：
7.7
作者：
Kulkarni RN;Mizrachi EB;Ocana AG;Stewart AF
通讯作者：
Stewart AF
影响因子：
7.7
作者：
Rankin MM;Kushner JA
通讯作者：
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影响因子：
11.8
作者：
Teta, Monica;Rankin, Matthew M.;Kushner, Jake A.
通讯作者：
Kushner, Jake A.
DOI：
10.3791/2166
发表时间：
2010-12-07
期刊：
Journal of visualized experiments : JoVE
影响因子：
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作者：
Tuttle, Alex H;Rankin, Matthew M;Kushner, Jake A
通讯作者：
Kushner, Jake A
DOI：
10.1152/ajpendo.00084.2012
发表时间：
2012-08-01
影响因子：
5.1
作者：
Ren, Gang;Kim, Ji Young;Smas, Cynthia M.
通讯作者：
Smas, Cynthia M.