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十二指肠空肠旁路手术后葡萄糖转运蛋白、糖异生和生物钟的变化。

Changes in glucose transporters, gluconeogenesis, and circadian clock after duodenal-jejunal bypass surgery.

作者信息

Kim Mikyung, Son Young Gil, Kang Yu Na, Ha Tae Kyung, Ha Eunyoung

机构信息

Department of Biochemistry, Pain Research Center, School of Medicine, Keimyung University, Daegu, South Korea.

出版信息

Obes Surg. 2015 Apr;25(4):635-41. doi: 10.1007/s11695-014-1434-4.

Abstract

BACKGROUND

Bariatric surgery improves obesity and ameliorates glucose tolerance. This study was conducted to evaluate circadian clocks, gluconeogenesis, and glucose transport changes in hepatic and intestinal tissues after duodenal-jejunal bypass (DJB) surgery in a rat model.

METHODS

Twenty-five rats were randomly assigned to either sham group (10 rats) or DJB group (15 rats). Food intake, body weight, blood glucose, and serum insulin levels were measured. Quantitative RT-PCR, immunoblot, and immunohistochemistry were used to analyze genes and proteins in the liver and intestine.

RESULTS

Food intake and body weight were not different between sham and DJB groups. Blood glucose level was significantly lower in the DJB group compared with that in the sham group. Although not significant, serum insulin level showed an increased tendency in DJB group. DJB induced marked expressions of glucose transporter-2 (GLUT2) in the liver and GLUT2 and sodium-dependent glucose transporter-1 (SGLT1) in the intestine. Gluconeogenic enzymes [phosphoenolpyruvate carboxykinase-1 (Pck1) and glucose-6-phosphatase (G6Pase)] decreased in the liver and increased in the intestine of the DJB group. Circadian transcription factor cryptochrome-1 (Cry1) increased in the liver and decreased in the intestine of the DJB group. Another circadian transcription factor period-2 (Per2) also increased in the liver and decreased in the intestine of the DJB group.

CONCLUSION

In conclusion, this study suggests the possibility that Cry1 and Per2 may mediate decreased gluconeogenesis in the liver and increased gluconeogenesis in the intestine of the DJB group.

摘要

背景

减肥手术可改善肥胖状况并改善糖耐量。本研究旨在评估大鼠模型十二指肠空肠旁路术(DJB)后肝脏和肠道组织中昼夜节律时钟、糖异生及葡萄糖转运的变化。

方法

将25只大鼠随机分为假手术组(10只大鼠)和DJB组(15只大鼠)。测量食物摄入量、体重、血糖和血清胰岛素水平。采用定量RT-PCR、免疫印迹和免疫组化分析肝脏和肠道中的基因和蛋白质。

结果

假手术组和DJB组的食物摄入量和体重无差异。DJB组的血糖水平显著低于假手术组。虽然差异不显著,但DJB组的血清胰岛素水平有升高趋势。DJB诱导肝脏中葡萄糖转运蛋白2(GLUT2)以及肠道中GLUT2和钠依赖性葡萄糖转运蛋白1(SGLT1)显著表达。糖异生酶[磷酸烯醇丙酮酸羧激酶-1(Pck1)和葡萄糖-6-磷酸酶(G6Pase)]在DJB组的肝脏中减少,在肠道中增加。昼夜节律转录因子隐花色素-1(Cry1)在DJB组的肝脏中增加,在肠道中减少。另一种昼夜节律转录因子周期蛋白-2(Per2)在DJB组的肝脏中也增加,在肠道中减少。

结论

总之,本研究提示Cry1和Per2可能介导DJB组肝脏中糖异生减少以及肠道中糖异生增加的可能性。

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