Elevation in tanis expression alters glucose metabolism and insulin sensitivity in H4IIE cells
Elevation in tanis expression alters glucose metabolism and insulin sensitivity in H4IIE cells
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DOI：
10.2337/diabetes.52.4.929
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发表时间：
2003-04-01
期刊：
影响因子：
7.7
通讯作者：
Collier, GR
中科院分区：
文献类型：
--
作者：
Gao, Y;Walder, K;Collier, GR
增加的肝葡萄糖输出和减少的葡萄糖利用与2型糖尿病的发展有关。我们先前报道了一个新的基因，Tanis，表达上调，在禁食期间在肥胖/糖尿病动物模型Psammomys obesus的肝脏。本文对该蛋白及其功能进行了进一步的研究。细胞分级分离表明Tanis定位于细胞膜和微粒体中，但不在细胞核、线粒体或可溶性蛋白部分中。与先前的基因表达数据一致，禁食后糖尿病肥胖大鼠肝脏Tanis蛋白水平比非糖尿病对照组显著增加。我们使用重组腺病毒来增加肝癌H4 IIE细胞中Tanis的表达，并研究其在代谢中的作用。Tanis过表达降低葡萄糖摄取、基础和胰岛素刺激的糖原合成和糖原含量，并减弱胰岛素对PEPCK基因表达的抑制，但不影响胰岛素刺激的胰岛素受体磷酸化或甘油三酯合成。这些结果表明Tanis可能参与葡萄糖代谢的调节，并且Tanis的表达增加可能有助于肝脏中的胰岛素抵抗。
Increased hepatic glucose output and decreased glucose utilization are implicated in the development of type 2 diabetes. We previously reported that the expression of a novel gene, Tanis, was upregulated in the liver during fasting in the obese/diabetic animal model Psammomys obesus. Here, we have further studied the protein and its function. Cell fractionation indicated that Tanis was localized in the plasma membrane and microsomes but not in the nucleus, mitochondria, or soluble protein fraction. Consistent with previous gene expression data, hepatic Tanis protein levels increased more significantly in diabetic P. obesus than in nondiabetic controls after fasting. We used a recombinant adenovirus to increase Tanis expression in hepatoma H4IIE cells and investigated its role in metabolism. Tanis overexpression reduced glucose uptake, basal and insulin-stimulated glycogen synthesis, and glycogen content and attenuated the suppression of PEPCK gene expression by insulin, but it did not affect insulin-stimulated insulin receptor phosphorylation or triglyceride synthesis. These results suggest that Tanis may be involved in the regulation of glucose metabolism, and increased expression of Tanis could contribute to insulin resistance in the liver.