Duodenal-Jejunal Bypass Ameliorates Type 2 Diabetes Mellitus by Activating Insulin Signaling and Improving Glucose Utilization in the Brain
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Duodenal-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.
A 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.
The 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.
These results indicate that enhanced brain insulin signaling transduction and brain glucose utilization play important roles in the antidiabetic effect of DJB.
KeywordsMetabolic surgery Brain insulin signaling Brain glucose metabolism Diabetic neuropathy
Type 2 diabetes mellitus
Protein kinase B
Glucose transporter type 1
Glucose transporter type 3
Insulin receptor substrate 1
Insulin receptor substrate 2
Authors would like to thank Jing-Yue Yan, PhD, candidate in the College of Pharmacy, Ohio State University, OH, 43210, USA, for editing and revising the manuscript.
Designed and led the study and wrote the manuscript: MQ, ZG. Performed the experiments and statistical analysis data: NL, QY, QJ, RP, HW, BJ, XL, JD, YW, XW, MZ, QM, XL, ZL. All co-authors commented on the manuscript and agreed with the manuscript results and conclusions.
MQ is funded by the National Natural Science Foundation of China (81871892), Natural Science Foundation of Shandong Province (ZR2015HL128), and Technology Development Plan of Weifang (2018YX027). ZG and MQ are funded by the National Natural Science Foundation of China (31671208). JD and MQ are funded by the Natural Science Foundation of China (81500798). ZL is funded by the Natural Science Foundation of China (81471048). XW is funded by the Natural Science Foundation of China (81503108).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
A Statement of Animal Rights
This study was carried out in accordance with the recommendations of Weifang Medical University, China. The experimental protocol was approved by the Research Ethics Committee of Weifang Medical University, China.
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