Affourtit Charles, Brand Martin D
MRC Dunn Human Nutrition Unit, Cambridge CB2 0XY, UK.
Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):973-9. doi: 10.1016/j.bbabio.2008.03.022. Epub 2008 Apr 3.
Pancreatic beta cells secrete insulin when blood glucose levels are high. Dysfunction of this glucose-stimulated insulin secretion (GSIS) is partly responsible for the manifestation of type 2 diabetes, a metabolic disorder that is rapidly becoming a global pandemic. Mitochondria play a central role in GSIS by coupling glucose oxidation to production of ATP, a signal that triggers a series of events that ultimately leads to insulin release. Beta cells express a mitochondrial uncoupling protein, UCP2, which is rather surprising as activity of such a protein is anticipated to lower the efficiency of oxidative phosphorylation, and hence to impair GSIS. The mounting evidence demonstrating that insulin secretion is indeed blunted by UCP2 agrees with this prediction, and has provoked the idea that UCP2 activity contributes to beta cell pathogenesis and development of type 2 diabetes. Although this notion may be correct, the evolved function of UCP2 remains unclear. With this paper we aim to provide a brief account of the present state of affairs in this field, suggest a physiological role for UCP2, and highlight some of our own recent results.
当血糖水平升高时，胰腺β细胞会分泌胰岛素。这种葡萄糖刺激的胰岛素分泌（GSIS）功能障碍是导致2型糖尿病（一种迅速成为全球大流行的代谢紊乱疾病）的部分原因。线粒体在GSIS中起着核心作用，它将葡萄糖氧化与ATP的产生相偶联，ATP作为一种信号触发一系列最终导致胰岛素释放的事件。β细胞表达一种线粒体解偶联蛋白UCP2，这相当令人惊讶，因为预计这种蛋白的活性会降低氧化磷酸化的效率，从而损害GSIS。越来越多的证据表明UCP2确实会使胰岛素分泌减少，这与这一预测相符，并引发了这样一种观点，即UCP2的活性促成了β细胞发病机制及2型糖尿病的发展。尽管这个观点可能是正确的，但UCP2的进化功能仍不清楚。在本文中，我们旨在简要介绍该领域的现状，提出UCP2的生理作用，并突出我们自己最近的一些研究结果。
