The plasma 5'-AMP acts as a potential upstream regulator of hyperglycemia in type 2 diabetic mice.
The plasma 5'-AMP acts as a potential upstream regulator of hyperglycemia in type 2 diabetic mice.
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DOI：
10.1152/ajpendo.00424.2011
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发表时间：
2012-02
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影响因子：
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通讯作者：
Ying Zhang;Zhongqi Wang;Yue Zhao;Ming-Hui Zhao;Shiming Wang;Z. Hua;Jianfa Zhang
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文献类型：
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作者：
Ying Zhang;Zhongqi Wang;Yue Zhao;Ming-Hui Zhao;Shiming Wang;Z. Hua;Jianfa Zhang
血浆游离脂肪酸 (FFA) 水平升高是 2 型糖尿病的标志。然而，FFA 引起的高血糖的分子基础仍不清楚。在这里，我们发现 2 型糖尿病小鼠血浆中的 5'-单磷酸腺苷 (pAMP) 显着升高。高水平的 FFA 会引起静脉内皮细胞损伤，并导致 pAMP 增加。给予合成 5'-AMP 会导致瘦野生型小鼠出现高血糖并损害胰岛素作用。 5'-AMP 可以提高腺苷受体缺陷小鼠的血糖，其效果与野生型小鼠相同。 pAMP 的功能是通过细胞腺苷水平升高启动的，直接刺激 G-6-Pase 酶活性，减弱骨骼肌中胰岛素依赖性 GLUT4 易位，并表现出血糖快速急剧升高和肝糖原水平降低。随后肝脏 Foxo1 及其靶向基因 Pepck 和 G6Pase 的基因表达增加，这与 db/db 小鼠的糖尿病表型相似。我们的结果表明 pAMP 是 2 型糖尿病高血糖的潜在上游调节因子。
Increased plasma free fatty acid (FFA) level is a hallmark of type 2 diabetes. However, the underlying molecular basis for FFA-caused hyperglycemia remains unclear. Here we identified plasma 5'-adenosine monophosphate (pAMP) markedly elevated in the plasma of type 2 diabetic mice. High levels of FFAs induced damage in vein endothelial cells and contributed to an increase in pAMP. Administration of synthetic 5'-AMP caused hyperglycemia and impaired insulin action in lean wild-type mice. 5'-AMP elevated blood glucose in mice deficient in adenosine receptors with equal efficiency as wild-type mice. The function of pAMP was initiated by the elevation of cellular adenosine levels, directly stimulating G-6-Pase enzyme activity, attenuating insulin-dependent GLUT4 translocation in skeletal muscle, and displaying a rapid and steep increase in blood glucose and a decrease in hepatic glycogen level. It was followed by an increase in the gene expression of hepatic Foxo1 and its targeting gene Pepck and G6Pase, which was similar to diabetic phenotype in db/db mice. Our results suggest that pAMP is a potential upstream regulator of hyperglycemia in type 2 diabetes.