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

  • Na Li
  • Qing-Tao Yan
  • Qi Jing
  • Rui-Yan Pan
  • Huai-Jie Wang
  • Bin Jiang
  • Xian-Jun Li
  • Yi Wang
  • Jun-Hong Dong
  • Xue-Jian Wang
  • Mei-Jia Zhang
  • Qing-Guo Meng
  • Xiang-Zhen Li
  • Zhi-Jun Liu
  • Zhi-Qin GaoEmail author
  • Mei-Hua QuEmail author
Original Contributions

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.

Keywords

Metabolic surgery Brain insulin signaling Brain glucose metabolism Diabetic neuropathy 

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

Notes

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.

Author 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.

Funding Information

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.

Supplementary material

11695_2019_4153_Fig5_ESM.png (574 kb)
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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Na Li
    • 1
  • Qing-Tao Yan
    • 1
    • 2
  • Qi Jing
    • 1
  • Rui-Yan Pan
    • 1
  • Huai-Jie Wang
    • 1
  • Bin Jiang
    • 1
    • 3
  • Xian-Jun Li
    • 2
  • Yi Wang
    • 3
  • Jun-Hong Dong
    • 1
    • 4
  • Xue-Jian Wang
    • 1
  • Mei-Jia Zhang
    • 1
  • Qing-Guo Meng
    • 5
  • Xiang-Zhen Li
    • 1
  • Zhi-Jun Liu
    • 1
    • 4
  • Zhi-Qin Gao
    • 3
    Email author
  • Mei-Hua Qu
    • 1
    Email author
  1. 1.Department of Pharmacology, Laboratory of Applied Pharmacology, College of PharmacyWeifang Medical UniversityWeifangChina
  2. 2.Weifang People’s HospitalWeifangChina
  3. 3.Department of Cell Biology, Laboratory of Bio-Pharmacy, School of Bioscience and TechnologyWeifang Medical UniversityWeifangChina
  4. 4.College of MedicineWeifang Medical UniversityWeifangChina
  5. 5.College of PharmacyYantai UniversityYantaiChina

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