Role of Proximal Intestinal Glucose Sensing and Metabolism in the Blood Glucose Control in Type 2 Diabetic Rats After Duodenal Jejunal Bypass Surgery

近端肠道葡萄糖传感与代谢在十二指肠空肠旁路手术后2型糖尿病大鼠血糖控制中的作用

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作者:Bin Jiang #, Huaijie Wang #, Na Li #, Qingtao Yan, Weiyu Wang, Yubing Wang, Hantao Xue, Shengyao Ma, Xiaocheng Li, Wenbin Diao, Ruiyan Pan, Zhiqin Gao, Mei-Hua Qu

Background

Although gastric surgery can significantly improve blood glucose homeostasis in type 2 diabetes mellitus (T2DM), its mechanism remains unclear. This study evaluated the role of intestinal glucose sensing, glucose transport, and metabolism in the alimentary limb (A limb) of T2DM rats after duodenal jejunal bypass (DJB) surgery.

Conclusion

Proximal intestinal glucose sensing and metabolism play an important role in blood glucose homeostasis by DJB.

Methods

A T2DM rat model was induced via a high-glucose high-fat diet and low-dose streptozotocin injection. The diabetic rats were divided into two groups: the DJB surgery (T2DM-DJB) group and the sham surgery (T2DM-Sham) group. Wistar rats were used as wild-type control (Control). Small animal PET was used to assess the change in glucose metabolic status in the intestine. The intestinal villi height and the number of EECs after DJB were evaluated. The expressions of sweet taste receptors (T1R2/T1R3), glucose transporters (SGLT1/GLUT2), and key enzymes involved in glucose metabolism (HK2, PFK2, PKM2, G6Pase, and PCK1) in the A limb after DJB was detected by Western blot and qRT-PCR.

Results

Small animal PET analysis showed the intestinal glucose metabolism increased significantly 6 weeks after DJB surgery. The intestinal villi height and the number of EECs in the A limb 6 weeks after surgery increased significantly in T2DM-DJB rats comparing to T2DM-Sham rats. The mRNA and protein expression of T1R1/T1R3 and SGLT1/GLUT2 were downregulated in DJB-T2DM rats, while enzymes involved in glucose metabolism was upregulated in the A limb in T2DM-DJB rats.

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