Adenosine signaling promotes regeneration of pancreatic β cells in vivo.
Adenosine signaling promotes regeneration of pancreatic β cells in vivo.
复制标题
DOI：
10.1016/j.cmet.2012.04.018
复制
发表时间：
2012-06-06
期刊：
影响因子：
29
通讯作者：
Stainier DY
中科院分区：
文献类型：
--
作者：
Andersson O;Adams BA;Yoo D;Ellis GC;Gut P;Anderson RM;German MS;Stainier DY
糖尿病可以通过注射胰岛素来控制，但仍然需要一种恢复产生胰岛素的β细胞数量的治疗方法。利用斑马鱼糖尿病模型，我们筛选了约7000个小分子来鉴定β细胞再生的促进剂。我们发现的化合物集中在腺苷信号通路上，包括外源性激动剂和抑制内源性腺苷降解的化合物。最有效的β-细胞再生促进剂是腺苷激动剂5 ' - n -乙基羧氨基腺苷（NECA），它通过腺苷受体A2aa作用于斑马鱼，增加β-细胞增殖，加速正常血糖的恢复。尽管在再生过程中显著刺激β细胞增殖，NECA在发育过程中只有适度的作用。在糖尿病小鼠中证实了NECA的增殖和降血糖作用，提示腺苷在β细胞再生中的进化保守作用。通过这种整体筛选，我们确定了腺苷途径的成分，可以作为治疗糖尿病的治疗靶点。
Diabetes can be controlled with insulin injections, but a curative approach that restores the number of insulin-producing β-cells is still needed. Using a zebrafish model of diabetes, we screened ~7000 small molecules to identify enhancers of β-cell regeneration. The compounds we identified converge on the adenosine signaling pathway and include exogenous agonists and compounds that inhibit degradation of endogenously produced adenosine. The most potent enhancer of β-cell regeneration was the adenosine agonist 5′-N-Ethylcarboxamidoadenosine (NECA), which acting through the adenosine receptor A2aa increased β-cell proliferation and accelerated restoration of normoglycemia in zebrafish. Despite markedly stimulating β-cell proliferation during regeneration, NECA had only a modest effect during development. The proliferative and glucose-lowering effect of NECA was confirmed in diabetic mice, suggesting an evolutionarily conserved role for adenosine in β-cell regeneration. With this whole-organism screen, we identified components of the adenosine pathway that could be therapeutically targeted for the treatment of diabetes.
登录
查看更多内容
影响因子：
7.7
作者：
Figler RA;Wang G;Srinivasan S;Jung DY;Zhang Z;Pankow JS;Ravid K;Fredholm B;Hedrick CC;Rich SS;Kim JK;LaNoue KF;Linden J
通讯作者：
Linden J
影响因子：
29
作者：
Porat, Shay;Weinberg-Corem, Noa;Dor, Yuval
通讯作者：
Dor, Yuval
影响因子：
64.8
作者：
Dor, Y;Brown, J;Melton, DA
通讯作者：
Melton, DA
影响因子：
64.5
作者：
Mondal BC;Mukherjee T;Mandal L;Evans CJ;Sinenko SA;Martinez-Agosto JA;Banerjee U
通讯作者：
Banerjee U
影响因子：
64.8
作者：
通讯作者：
--