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
ARTICLE HIGHLIGHTS
Research background

The results showed that after vascular endothelial growth factor B (VEGFB) overexpression, serum glucose, glucose tolerance, and insulin sensitivity in impaired glucose tolerance (IGT) mice were improved, and the number of secretory granules of β cells was increased by activating the PI3K/AKT signal pathway.

Research motivation

VEGFB can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to improve glucose metabolism in mice with IGT.

Research objectives

This study illustrated the role of VEGFB in regulating insulin-mediated glucagon secretion in mice with IGT by regulating the PI3K/AKT signal pathway, which indicated the regulatory function of VEGFB in improving the IGT condition of mice and preventing the onset of type 2 diabetes in the body. This study proved the molecular mechanism of VEGFB regulating IGT and provided theoretical basis for the treatment of prediabetes.

Research methods

The research was conducted by Crispr Cas9 and high-fat diet feeding to construct the animal model. Western blot and qRT-PCR were used to detect the expression of proteins and genes. Bioinformatics was used to analyze the correlation between relative proteins in the PI3K/AKT signal pathway.

Research results

To specify the underlying mechanism of VEGFB effects on insulin-mediated glucagon secretion in impaired glucose tolerance.

Research conclusions

Type 2 diabetes (T2D) can be prevented in pre-diabetic individuals with impaired glucose tolerance. Therefore, converting IGT into a normal condition is critical to prevent the onset of diabetes.

Research perspectives

Diabetes is a worldwide health problem, affecting about 415 million people globally. Among them, the number of patients with type 2 diabetes accounts for about 90% of the number of patients with diabetes with a population of 373 million. Pre-diabetes is the main risk factor for progression to type 2 diabetes. Impaired glucose tolerance (IGT) is a pre-diabetes state, and it is mainly manifested as fast blood glucose (FBG) level of<7.0 mmol/L and/or posttraumatic blood glucose (PBG) level of 7.8 – 11.1 mmol/L after 2 h of oral glucose administration. Long-term IGT will greatly increase the risk of type 2 diabetes. Therefore, precision intervention can improve the insulin sensitivity of patients with IGT and effectively prevent or delay the progression to type 2 diabetes. VEGFB, as a novel metabolic regulatory target, has received much attention for its role in regulating insulin sensitivity. Therefore, we successfully constructed a mouse model with IGT, and intervened in the upregulation and downregulation of the VEGFB gene at the gene level, so as to explore that VEGFB regulates insulin-mediated Glucagon secretion, and thus improves IGT symptoms in pre-diabetes.