Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2023; 14(11): 1643-1658
Published online Nov 15, 2023. doi: 10.4239/wjd.v14.i11.1643
Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion
Yu-Qi Li, Lu-Yang Zhang, Yu-Chi Zhao, Fang Xu, Zhi-Yong Hu, Qi-Hao Wu, Wen-Hao Li, Ya-Nuo Li
Yu-Qi Li, Fang Xu, Wen-Hao Li, Ya-Nuo Li, Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, Yantai 264000, Shandong Province, China
Lu-Yang Zhang, Department of Rheumatology and Immunology, Yantaishan Hospital, Yantai 264000, Shandong Province, China
Yu-Chi Zhao, Department of Surgery, Yantaishan Hospital, Yantai 264000, Shandong Province, China
Zhi-Yong Hu, School of Public Health and Management, Binzhou Medical University, Yantai 264000, Shandong Province, China
Qi-Hao Wu, The First School of Clinical Medicine, Binzhou Medical University, Yantai 264000, Shandong Province, China
Author contributions: Li YQ and Li YN conceived and designed the study; Zhang LY, Zhao YC, and Xu F performed the experiments; Hu ZY and Wu QH analyzed the data; Li YQ wrote the manuscript; Li WH revised the manuscript; and all authors approved the final version of the article.
Supported by the National Natural Science Foundation of China, No. 31771284; Basic Research Project of Yantai Science and Technology Innovation and Development Plan, No. 2022JCYJ026; Natural Science Foundation of Shandong province, No. ZR202111250163; and Yantai Science and Technology Plan Project, No. 2022YD062.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Ethics Committee of Binzhou Medical University (Approval No. 2023-170).
Conflict-of-interest statement: The authors have declared no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at liyanuo@bzmc.edu.cn.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ya-Nuo Li, PhD, Professor, Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, No. 346 Guanhai Road, Laishan District, Yantai 264000, Shandong Province, China. liyanuo@bzmc.edu.cn
Received: March 28, 2023
Peer-review started: March 28, 2023
First decision: July 4, 2023
Revised: July 11, 2023
Accepted: September 6, 2023
Article in press: September 6, 2023
Published online: November 15, 2023
Processing time: 230 Days and 17.7 Hours
Abstract
BACKGROUND

Impaired glucose tolerance (IGT) is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes. When IGT occurs, insulin sensitivity decreases, causing a reduction in insulin secretion and an increase in glucagon secretion. Recently, vascular endothelial growth factor B (VEGFB) has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity. Therefore, we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion, thus contributing to the prevention and cure of prediabetes.

AIM

To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.

METHODS

We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression. Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay, and the protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) was determined using western blot. Further, mRNA expression of forkhead box protein O1, phosphoenolpyruvate carboxykinase, and glucose-6 phosphatase was detected via quantitative polymerase chain reaction, and the correlation between the expression of proteins was analyzed via bioinformatics.

RESULTS

In mice with IGT and VEGFB knockout, glucagon secretion increased, and the protein expression of PI3K/AKT decreased dramatically. Further, in mice with VEGFB overexpression, glucagon levels declined, with the activation of the PI3K/AKT signaling pathway.

CONCLUSION

VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

Keywords: Vascular endothelial growth factor B; Insulin-mediated; Glucagon secretion; Prediabetes; Impaired glucose tolerance

Core Tip: Impaired glucose tolerance (IGT) is an abnormal metabolic stage between the normal state and diabetes, which belongs to prediabetes. Therefore, intervention in IGT can effectively reduce the incidence rate of diabetes. The pathological mechanism of IGT is related to glucose homeostasis imbalance and decreased insulin sensitivity. Currently, vascular endothelial growth factor B (VEGFB) has been reported to have the effect of restoring glucose tolerance and improving insulin sensitivity. Therefore, the use of VEGFB as a target for intervention has become the focus of current research. This research mainly illustrates the role of VEGFB in promoting insulin and glucagon secretion to alleviate IGT and its potential molecular mechanism.