UCP2 is highly expressed in pancreatic α-cells and influences secretion and survival
UCP2 is highly expressed in pancreatic α-cells and influences secretion and survival
复制标题
DOI：
10.1073/pnas.0710434105
复制
发表时间：
2008-08-19
影响因子：
11.1
通讯作者：
Wheeler, Michael B.
中科院分区：
文献类型：
--
作者：
Diao, Jingyu;Allister, Emma M.;Wheeler, Michael B.
在胰腺β细胞中，解偶联蛋白2（UCP 2）影响线粒体氧化磷酸化和胰岛素分泌。在这里，我们发现α细胞表达的UCP 2水平显著高于β细胞。与p细胞相比，在a细胞中观察到更大的线粒体UCP 2相关解偶联，并伴有较低的氧化磷酸化效率（ATP/O）。相反，降低α-细胞中的UCP 2活性与葡萄糖氧化产生的更高的线粒体膜电位和增加的ATP合成相关，表明更有效的代谢偶联。在体外，UCP 2活性的抑制导致低血糖时胰高血糖素分泌减少;然而，在体内，UCP 2（-/-）小鼠的空腹胰高血糖素水平正常。除了其对分泌的作用外，UCP 2在胰岛中还起细胞保护作用，其中UCP 2（-/-）α-细胞对特异性死亡刺激更敏感。总之，我们证明了UCP 2在维持α-细胞在葡萄糖代谢、胰高血糖素分泌和细胞保护水平上的功能中的直接作用。
In pancreatic beta-cells, uncoupling protein 2 (UCP2) influences mitochondrial oxidative phosphorylation and insulin secretion. Here, we show that a-cells express significantly higher levels of UCP2 than do beta-cells. Greater mitochondrial UCP2-related uncoupling was observed in a-cells compared with p-cells and was accompanied by a lower oxidative phosphorylation efficiency (ATP/O). Conversely, reducing UCP2 activity in a-cells was associated with higher mitochondrial membrane potential generated by glucose oxidation and with increased ATP synthesis, indicating more efficient metabolic coupling. In vitro, the suppression of UCP2 activity led to reduced glucagon secretion in response to low glucose; however, in vivo, fasting glucagon levels were normal in UCP2(-/-) mice. in addition to its effects on secretion, UCP2 played a cytoprotective role in islets, with UCP2(-/-) alpha-cells being more sensitive to specific death stimuli. In summary, we demonstrate a direct role for UCP2 in maintaining a-cell function at the level of glucose metabolism, glucagon secretion, and cytoprotection.