Li Zhiwei, Sun Fei, Zhang Yaohui, Chen Hao, He Ningning, Chen Hui, Song Penghong, Wang Yan, Yan Sheng, Zheng Shusen
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
PLoS One. 2015 Nov 23;10(11):e0143405. doi: 10.1371/journal.pone.0143405. eCollection 2015.
The use of the immunosuppressive drug tacrolimus (TAC) is related to new onset diabetes after transplantation. Herein, we examined the effect of intraperitoneal administered TAC on intestinal glucose absorption in mice.
Animals received low, medium, or high dose TAC (0.5, 1, or 5 mg/kg/d, respectively), or 0.9% saline solution (control) for 14 days. Oral glucose tolerance test (OGTT), insulin concentration test, and serum TAC concentration measurements was performed after 14 days of TAC exposure. Plasma insulin was assessed and electrogenic glucose absorption were measured by the sodium-dependent increase of the short-circuit current. Expression levels of the glucose transporters sodium glucose co-transporter (SGLT) 1, glucose transporter (GLUT) 2, and GLUT5 were also determined.
Oral glucose absorption assessed by OGTT was significantly enhanced in the low, medium, and high groups. Serum insulin was elevated in the medium and high group compared with the control. Moreover, glucose-induced Isc was significantly higher in TAC administrated groups, which indicates that SGLT1 activity increased. Transcription levels and protein abundance of SGLT1 in the experimental groups also increased compared with the control.
TAC induced insulin resistance and strengthened intestinal glucose absorption by increasing the activity and expression of the glucose transporter, SGLT1.
免疫抑制药物他克莫司（TAC）的使用与移植后新发糖尿病有关。在此，我们研究了腹腔注射TAC对小鼠肠道葡萄糖吸收的影响。
动物分别接受低、中、高剂量的TAC（分别为0.5、1或5mg/kg/d）或0.9%盐溶液（对照），持续14天。在TAC暴露14天后进行口服葡萄糖耐量试验（OGTT）、胰岛素浓度测试和血清TAC浓度测量。评估血浆胰岛素，并通过钠依赖性短路电流增加来测量电生性葡萄糖吸收。还测定了葡萄糖转运蛋白钠葡萄糖协同转运蛋白（SGLT）1、葡萄糖转运蛋白（GLUT）2和GLUT5的表达水平。
通过OGTT评估，低、中、高剂量组的口服葡萄糖吸收均显著增强。与对照组相比，中、高剂量组的血清胰岛素升高。此外，TAC给药组的葡萄糖诱导的短路电流显著更高，这表明SGLT1活性增加。与对照组相比，实验组中SGLT1的转录水平和蛋白丰度也增加。
TAC通过增加葡萄糖转运蛋白SGLT1的活性和表达诱导胰岛素抵抗并增强肠道葡萄糖吸收。
