肠上皮胰岛素信号在全身葡萄糖及脂质平衡中发挥重要作用

Authors

Siegfried Ussar PhD

The intestinal mucosa has a dual function in providing a specialized epithelium as a barrier to prevent microbial invasion and to facilitate absorption of nutrients. The insulin receptor is expressed throughout the cell surface of intestinal epithelial cells but its function in these specific cells is not fully understood. Some studies indicate a role for intestinal insulin signaling in glucose absorption while others suggest a role in the suppression of chylomicrons and thereby the modulation of whole body lipid homeostasis. To dissect the role of insulin signaling in the intestinal epithelium we generated mice lacking the insulin receptor specifically in the intestinal epithelium by crossing C57BL/6 insulin receptor floxed mice with mice expressing cre-recombinase under the villin promoter (VILIRKO). VILIRKO mice were born in a normal Mendelian ratio were fertile and showed no obvious developmental or metabolic abnormalities on a chow diet. In contrast when fed a high fat diet VILIRKO mice exhibited reduced body weight (53.5 ± 1.3g vs. 44.4 ± 3.9g) and improved oral glucose tolerance when compared to control littermates. In addition VILIRKO mice showed strongly reduced hepatic steatosis. This was accompanied by reduced serum triglyceride levels as well as a trend to reduced cholesterol levels. Interestingly VILIRKO mice had increased visceral but not subcutaneous adipose tissue. Circulating resistin levels were also increased whereas circulating leptin levels remained unchanged. These data indicate that intestinal epithelial insulin signaling has an important role in the regulation of whole body metabolism insulin sensitivity and fat distribution and could be an important extrinsic regulator of hepatic lipid metabolism.

编辑： 霄雁    来源：丁香园