Duodenal-Jejunal Bypass Ameliorates Type 2 Diabetes Mellitus by Activating Insulin Signaling and Improving Glucose Utilization in the Brain
Duodenal-Jejunal Bypass Ameliorates Type 2 Diabetes Mellitus by Activating Insulin Signaling and Improving Glucose Utilization in the Brain
复制标题
十二指肠空肠旁路术通过激活胰岛素信号传导和改善大脑中的葡萄糖利用来改善 2 型糖尿病
DOI：
10.1007/s11695-019-04153-3
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发表时间：
2019-10-11
期刊：
影响因子：
2.9
通讯作者：
Qu, Mei-Hua
中科院分区：
文献类型：
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作者：
Li, Na;Yan, Qing-Tao;Qu, Mei-Hua
背景十二指肠空肠旁路术 (DJB) 可以显着改善 2 型糖尿病，与体重减轻和食物限制无关。越来越多的证据表明，大脑胰岛素信号传导在 2 型糖尿病的病理生理学中发挥着重要作用。本研究探讨DJB的抗糖尿病作用是否与脑胰岛素信号激活和脑葡萄糖利用有关。方法采用高脂高糖饮食建立糖尿病大鼠模型。对糖尿病大鼠进行 DJB 或假手术。 18F-FDG PET 扫描用于检测不同器官（特别是大脑）的葡萄糖摄取。评估和分析脑组织中葡萄糖转运蛋白、葡萄糖利用相关蛋白（HK1和PFK2）、胰岛素和胰岛素信号通路相关蛋白（InsR、IRS1/2、PI3K和p-Akt）的水平。 结果结果显示，DJB显着改善2型糖尿病大鼠的基础血糖参数，并逆转了大脑中葡萄糖摄取的下降。 DJB 不仅显着增加脑胰岛素、IRS1/2、PI3K 和 p-Akt 的表达水平，还显着增加大脑中葡萄糖利用酶 HK1 和 PFK2 的水平。结论这些结果表明，增强的脑胰岛素信号转导和脑葡萄糖利用在 DJB 的抗糖尿病作用中发挥着重要作用。
BackgroundDuodenal-jejunal bypass (DJB) can dramatically improve type 2 diabetes independent of weight loss and food restriction. Increasing evidence has demonstrated that brain insulin signaling plays an important role in the pathophysiology of type 2 diabetes. This study explores whether the antidiabetic effect of DJB is involved in brain insulin signaling activation and brain glucose utilization.MethodsA diabetic rat model was established by high-fat and high-glucose diet. DJB or sham surgery was performed in diabetic rats. 18F-FDG PET scanning was used to detect glucose uptake in different organs, particularly in the brain. The levels of glucose transporters, glucose utilization-related proteins (HK1 and PFK2), insulin, and insulin signaling pathway-related proteins (InsR, IRS1/2, PI3K, and p-Akt) in the brain tissues were evaluated and analyzed.ResultsThe results showed that DJB significantly improved basal glycemic parameters and reversed the decreasing glucose uptake in the brains of type 2 diabetic rats. DJB significantly increased not only the expression levels of brain insulin, IRS1/2, PI3K, and p-Akt but also the levels of the glucose utilization enzymes HK1 and PFK2 in the brain.ConclusionThese results indicate that enhanced brain insulin signaling transduction and brain glucose utilization play important roles in the antidiabetic effect of DJB.