Differential role of SH2-B and APS in regulating energy and glucose homeostasis
Differential role of SH2-B and APS in regulating energy and glucose homeostasis
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DOI：
10.1210/en.2005-1313
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发表时间：
2006-05-01
期刊：
影响因子：
4.8
通讯作者：
Rui, L
中科院分区：
文献类型：
--
作者：
Li, M;Ren, DC;Rui, L
SH2- b和APS是pleckstrin同源和含SH2结构域适配器家族的两个成员，在培养细胞中以类似的方式促进胰岛素和瘦素信号传导。此外，APS介导胰岛素刺激的c-Cbl/CAP/TC10通路在培养脂肪细胞中的激活。在这里，我们对缺乏SH2-B、APS或两者都缺乏的转基因小鼠进行了表征，以确定这两种蛋白在动物中的生理作用。SH2-B基因的破坏导致肥胖、高血糖、高胰岛素血症和葡萄糖耐受不良。相反，APS基因的缺失不会改变肥胖、能量平衡和葡萄糖代谢。能量摄入、能量消耗、脂肪含量、体重、血浆胰岛素、瘦素、葡萄糖和脂质水平在喂食正常食物或高脂肪食物的APS（-/-）和WT幼崽之间相似。此外，APS的缺失并不能改变胰岛素和葡萄糖耐量。APS(-/-)/SH2-B-/-双敲除小鼠还出现能量失衡、肥胖、高瘦素血症、高胰岛素血症、高血糖和葡萄糖耐受不良；然而，APS(-/-)/SH2-B-/-小鼠血浆瘦素和胰岛素水平明显低于SH2-B-/-小鼠。这些结果表明SH2-B是小鼠能量和葡萄糖代谢的关键正调节因子，而不是APS。
SH2-B and APS, two members of a pleckstrin homology and SH2 domain-containing adaptor family, promote both insulin and leptin signaling in a similar fashion in cultured cells. In addition, APS mediates insulin-stimulated activation of the c-Cbl/CAP/TC10 pathway in cultured adipocytes. Here we characterized genetically modified mice lacking SH2-B, APS, or both to determine the physiological roles of these two proteins in animals. Disruption of the SH2-B gene resulted in obesity, hyperglycemia, hyperinsulinemia, and glucose intolerance. Conversely, deletion of the APS gene did not alter adiposity, energy balance, and glucose metabolism. Energy intake, energy expenditure, fat content, body weight, and plasma insulin, leptin, glucose, and lipid levels were similar between APS(-/-) and WT littermates fed either normal chow or a high-fat diet. Moreover, deletion of APS failed to alter insulin and glucose tolerance. APS(-/-)/SH2-B-/- double knockout mice also developed energy imbalance, obesity, hyperleptinemia, hyperinsulinemia, hyperglycemia, and glucose intolerance; however, plasma leptin and insulin levels were significantly lower in APS(-/-)/SH2-B-/- than in SH2-B-/- mice. These results suggest that SH2-B, but not APS, is a key positive regulator of energy and glucose metabolism in mice.