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

Obes Surg. 2020 Jan;30(1):279-289. doi: 10.1007/s11695-019-04153-3.

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: Brain glucose metabolism; Brain insulin signaling; Diabetic neuropathy; Metabolic surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Brain / metabolism*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / surgery
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / surgery*
  • Duodenum / pathology
  • Duodenum / surgery*
  • Gastric Bypass / methods*
  • Glucose / metabolism*
  • Insulin / metabolism*
  • Insulin Resistance / physiology
  • Jejunum / pathology
  • Jejunum / surgery*
  • Liver / metabolism
  • Male
  • Rats
  • Rats, Wistar
  • Signal Transduction / physiology
  • Treatment Outcome
  • Weight Loss

Substances

  • Blood Glucose
  • Insulin
  • Glucose