Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China.
FEBS Lett. 2012 May 7;586(9):1306-11. doi: 10.1016/j.febslet.2012.03.034. Epub 2012 Apr 5.
The existence of peripheral oscillators has been shown, and they are critically important for organizing the metabolism of the whole body. Here we show that mice deficient in mPer2 markedly increase circulatory levels of insulin compared with wild type mice. Insulin secretion was more effectively stimulated by glucose, and alloxan, a glucose analogue, induced more severe hyperglycemia in mPer2-deficient mice. Hepatic insulin degrading enzyme (Ide) displayed an obvious day and night rhythm, which was impaired in mPer2-deficient mice, leading to a decrease in insulin clearance. Deficiency in mPer2 caused increased Clock expression and decreased expression of Mkp1 and Ide1, possibly underlying the observed phenotypes and suggesting that mPer2 plays a role in regulation of circulating insulin levels.
现已证实外周振荡器的存在，其对全身新陈代谢的组织至关重要。在这里，我们发现相对于野生型小鼠，mPer2 缺失的小鼠其循环胰岛素水平明显升高。葡萄糖刺激胰岛素分泌的效果更明显，葡萄糖类似物——别嘌呤醇诱导 mPer2 缺失的小鼠发生更严重的高血糖症。肝胰岛素降解酶（Ide）呈现明显的昼夜节律，在 mPer2 缺失的小鼠中受到损害，导致胰岛素清除率下降。mPer2 的缺失导致 Clock 表达增加和 Mkp1 和 Ide1 表达减少，可能是导致观察到的表型的原因，并表明 mPer2 在调节循环胰岛素水平中发挥作用。
