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Duodenal-Jejunal Bypass Ameliorates Type 2 Diabetes Mellitus by Activating Insulin Signaling and Improving Glucose Utilization in the Brain

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

These results indicate that enhanced brain insulin signaling transduction and brain glucose utilization play important roles in the antidiabetic effect of DJB.

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Abbreviations

DJB:

Duodenal-jejunal bypass

T2DM:

Type 2 diabetes mellitus

PI3K:

Phosphoinositide 3-kinase

Akt:

Protein kinase B

p-Akt:

Phosphorylated Akt

GLUT1:

Glucose transporter type 1

GLUT3:

Glucose transporter type 3

HK1:

Hexokinase 1

PFK2:

Phosphofructokinase 2

InsR:

Insulin receptor

IRS1:

Insulin receptor substrate 1

IRS2:

Insulin receptor substrate 2

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Acknowledgments

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.

Funding

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).

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Author notes

  1. Na Li, Qing-Tao Yan and Qi Jing contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, Laboratory of Applied Pharmacology, College of Pharmacy, Weifang Medical University, 7166 Baotong West Street, Weifang, 261053, China

    Na Li, Qing-Tao Yan, Qi Jing, Rui-Yan Pan, Huai-Jie Wang, Bin Jiang, Jun-Hong Dong, Xue-Jian Wang, Mei-Jia Zhang, Xiang-Zhen Li, Zhi-Jun Liu & Mei-Hua Qu

  2. Weifang People’s Hospital, Weifang, 261041, China

    Qing-Tao Yan & Xian-Jun Li

  3. Department of Cell Biology, Laboratory of Bio-Pharmacy, School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, China

    Bin Jiang, Yi Wang & Zhi-Qin Gao

  4. College of Medicine, Weifang Medical University, Weifang, 261053, China

    Jun-Hong Dong & Zhi-Jun Liu

  5. College of Pharmacy, Yantai University, Yantai, 251041, China

    Qing-Guo Meng

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  1. Na Li
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Contributions

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.

Corresponding authors

Correspondence to Zhi-Qin Gao or Mei-Hua Qu.

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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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Supplemental Figure

A schematic model showing that DJB improves type 2 diabetes by increasing brain insulin and activating brain insulin signaling and glucose metabolism. DJB increases brain insulin levels and activates insulin signaling by increasing the expression levels of IRS1/IRS2, PI3K-Akt, HK1 and PFK2. DJB also increases the expression of GLUT3 and glucose uptake in the brain. These changes improve glucose aerobic oxidation and provide ATP for brain activities. (PNG 574 kb)

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Li, N., Yan, QT., Jing, Q. et al. Duodenal-Jejunal Bypass Ameliorates Type 2 Diabetes Mellitus by Activating Insulin Signaling and Improving Glucose Utilization in the Brain. OBES SURG 30, 279–289 (2020). https://doi.org/10.1007/s11695-019-04153-3

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