Nutrition Department, University of California Davis, Davis, CA 95616, USA.
Metabolism. 2011 Aug;60(8):1193-201. doi: 10.1016/j.metabol.2011.01.004. Epub 2011 Feb 25.
The SH2 domain-containing protein-tyrosine phosphatase Src homology phosphatase 2 (Shp2) has been implicated in a variety of growth factor signaling pathways, but its metabolic role in some peripheral insulin-responsive tissues remains unknown. To address the metabolic function of Shp2 in adipose tissue, we generated mice with adipose-specific Shp2 deletion using adiponectin-Cre transgenic mice. We then analyzed insulin sensitivity, glucose tolerance, and body mass in adipose-specific Shp2-deficient and control mice on regular chow and high-fat diet (HFD). Control mice on HFD exhibited increased Shp2 expression in various adipose depots compared with those on regular chow. Adiponectin-Cre mice enabled efficient and specific deletion of Shp2 in adipose tissue. However, adipose Shp2 deletion did not significantly alter body mass in mice on chow or HFD. In addition, mice with adipose Shp2 deletion exhibited comparable insulin sensitivity and glucose tolerance compared with controls. Consistent with this, basal and insulin-stimulated Erk and Akt phosphorylations were comparable in adipose tissue of Shp2-deficient and control mice. Our findings indicate that adipose-specific Shp2 deletion does not significantly alter systemic insulin sensitivity and glucose homeostasis.
含 SH2 结构域的蛋白酪氨酸磷酸酶 Src 同源磷酸酶 2（Shp2）参与多种生长因子信号通路，但它在一些外周胰岛素反应组织中的代谢作用尚不清楚。为了研究 Shp2 在脂肪组织中的代谢功能，我们利用脂联素-Cre 转基因小鼠生成了脂肪组织特异性 Shp2 缺失的小鼠。然后，我们在常规饲料和高脂肪饮食（HFD）上分析了脂肪组织特异性 Shp2 缺陷和对照小鼠的胰岛素敏感性、葡萄糖耐量和体重。与常规饲料相比，HFD 上的对照小鼠各种脂肪组织中的 Shp2 表达增加。脂联素-Cre 小鼠能够在脂肪组织中有效且特异性地缺失 Shp2。然而，脂肪组织 Shp2 缺失在 Chow 或 HFD 上的小鼠体重没有明显改变。此外，与对照组相比，脂肪组织 Shp2 缺失的小鼠胰岛素敏感性和葡萄糖耐量相当。与此一致的是，Shp2 缺陷和对照小鼠脂肪组织中的基础和胰岛素刺激的 Erk 和 Akt 磷酸化相当。我们的研究结果表明，脂肪组织特异性 Shp2 缺失不会显著改变全身胰岛素敏感性和葡萄糖稳态。
