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空肠-回肠旁路手术通过调节早期糖代谢改善大鼠 2 型糖尿病

Duodenal-Jejunal Exclusion Surgery Improves Type 2 Diabetes in a Rat Model Through Regulation of Early Glucose Metabolism.

机构信息

Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Endocrinology, the Dezhou People's Hospital, Dezhou, China.

出版信息

Can J Diabetes. 2020 Jul;44(5):401-406.e1. doi: 10.1016/j.jcjd.2020.02.002. Epub 2020 Apr 9.

Abstract

OBJECTIVES

Metabolic surgery has been proven to be widely effective for the control of glucose and weight in patients with type 2 diabetes and obesity. However, the effects of bariatric surgery on nonobesity type 2 diabetes and its metabolism are still unclear. This study aimed to measure the effects of duodenal-jejunal exclusion on glycometabolism in nonobese rats with type 2 diabetes and to investigate its mechanisms.

METHODS

Goto-Kakizaki rats and Sprague-Dawley rats were divided into duodenal-jejunal exclusion operation groups and sham operation groups, respectively. The glucose-relative parameters were measured before and after operation. Eight weeks postoperation, the levels of the key regulators of intestinal gluconeogenesis and the crucial proteins of hepatic insulin signalling were evaluated.

RESULTS

Postoperatively, the concentrations of blood glucose declined, and the insulin sensitivity increased significantly in rats with diabetes. However, there was no obvious reduction in weight. Eight weeks postoperatively, the mRNA levels of glucose-6-phosphatase and phosphoenolpyruvate pyruvate kinase in the jejunum and the levels of insulin receptor substrate-2 and glucose transporter-2 in the liver were significantly increased compared with the rats that had undergone the sham operation.

CONCLUSIONS

Duodenal-jejunal exclusion surgery is an effective procedure for improving glucose metabolism independent of weight loss in nonobese rats with diabetes. The molecular mechanisms might be associated with a series of processes, including intestinal gluconeogenesis and the hepatic insulin signaling pathway.

摘要

目的

代谢手术已被证明对 2 型糖尿病和肥胖患者的血糖和体重控制具有广泛的疗效。然而,减重手术对非肥胖 2 型糖尿病及其代谢的影响仍不清楚。本研究旨在测量十二指肠空肠旁路术对非肥胖 2 型糖尿病大鼠糖代谢的影响,并探讨其机制。

方法

将 Goto-Kakizaki 大鼠和 Sprague-Dawley 大鼠分为十二指肠空肠旁路手术组和假手术组,分别在手术前后测量血糖相关参数。术后 8 周,评估肠糖异生关键调节因子和肝胰岛素信号关键蛋白的水平。

结果

术后糖尿病大鼠血糖浓度下降,胰岛素敏感性显著升高,但体重无明显减轻。术后 8 周,空肠葡萄糖-6-磷酸酶和磷酸烯醇丙酮酸丙酮酸激酶的 mRNA 水平以及肝胰岛素受体底物-2 和葡萄糖转运体-2 的水平均明显高于假手术组大鼠。

结论

十二指肠空肠旁路术是一种有效的改善葡萄糖代谢的方法,与非肥胖型糖尿病大鼠的体重减轻无关。其分子机制可能与一系列过程有关,包括肠糖异生和肝胰岛素信号通路。

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