Na Li1, Qing-Tao Yan1,2, Qi Jing1, Rui-Yan Pan1, Huai-Jie Wang1, Bin Jiang1,3, Xian-Jun Li2, Yi Wang3, Jun-Hong Dong1,4, Xue-Jian Wang1, Mei-Jia Zhang1, Qing-Guo Meng5, Xiang-Zhen Li1, Zhi-Jun Liu1,4, Zhi-Qin Gao6, Mei-Hua Qu7. 1. Department of Pharmacology, Laboratory of Applied Pharmacology, College of Pharmacy, Weifang Medical University, 7166 Baotong West Street, Weifang, 261053, China. 2. Weifang People's Hospital, Weifang, 261041, China. 3. Department of Cell Biology, Laboratory of Bio-Pharmacy, School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, China. 4. College of Medicine, Weifang Medical University, Weifang, 261053, China. 5. College of Pharmacy, Yantai University, Yantai, 251041, China. 6. Department of Cell Biology, Laboratory of Bio-Pharmacy, School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, China. zhiqingao2013@163.com. 7. Department of Pharmacology, Laboratory of Applied Pharmacology, College of Pharmacy, Weifang Medical University, 7166 Baotong West Street, Weifang, 261053, China. qumeihua2016@163.com.
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.
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 diabeticrat model was established by high-fat and high-glucose diet. DJB or sham surgery was performed in diabeticrats. 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 diabeticrats. 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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