Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2021; 12(4): 480-498
Published online Apr 15, 2021. doi: 10.4239/wjd.v12.i4.480
Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca2+ and cyclic adenosine monophosphate levels through PI3K/AKT pathway
Jing-Dan Jia, Wen-Guo Jiang, Xu Luo, Rong-Rong Li, Yu-Chi Zhao, Geng Tian, Ya-Na Li
Jing-Dan Jia, Xu Luo, Rong-Rong Li, Ya-Na Li, Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, Yantai 264003, Shandong Province, China
Wen-Guo Jiang, Geng Tian, Department of Pharmacy, Binzhou Medical University, Yantai 264003, Shandong Province, China
Yu-Chi Zhao, Department of Surgery, Yantaishan Hospital, Yantai 264001, Shandong Province, China
Author contributions: Li YN and Tian G conceived and designed the study; Jia JD, Luo X, and Li RR performed the experiments; Jiang WG and Zhao YC analyzed the data; Jia JD wrote the manuscript; Li YN revised the manuscript; all authors approved the final version of the article.
Supported by National Natural Science Foundation of China, No. 31771284; National Natural Science Foundation of China Youth Project, No. 31702024; Major Basic Research Project of Shandong Provincial Natural Science Foundation, No. ZR2019ZD27; and Shandong Province Higher Educational Science and Technology Plan Project, No. J17KA258.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Binzhou Medical University.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Medical Ethics Committee of Binzhou Medical University (IACUC protocol number: 2017-018).
Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
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:
Corresponding author: Ya-Na Li, PhD, Associate Professor, Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, No. 346 Guanhai Road, Laishan District, Yantai 264003, Shandong Province, China.
Received: December 8, 2020
Peer-review started: December 8, 2020
First decision: January 11, 2021
Revised: January 25, 2021
Accepted: March 8, 2021
Article in press: March 8, 2021
Published online: April 15, 2021

Type 2 diabetes (T2D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance, resulting in an increase in blood glucose. However, the mechanism involved in this lack of insulin secretion is unclear. The level of vascular endothelial growth factor B (VEGF-B) is significantly increased in T2D patients. The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation. It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin. As an in vitro model of normal pancreatic β-cells, the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.


To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.


The MIN6 mouse pancreatic islet β-cell line was used as the model system. By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells, we examined the effects of VEGF-B on insulin secretion, Ca2+ and cyclic adenosine monophosphate (cAMP) levels, and the insulin secretion signaling pathway.


Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells. Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1 (PLCγ1), phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase (AKT), and other proteins in the insulin secretion pathway. Upon knockdown of VEGF-B, MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1, PI3K, AKT, and other proteins.


VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP. VEGF-B involvement in insulin secretion is related to the expression of PLCγ1, PI3K, AKT, and other signaling proteins. These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2D.

Keywords: Type 2 diabetes, Insulin secretion, MIN6 cells, Vascular endothelial growth factor B, Blood glucose regulation

Core Tip: Type 2 diabetes has elicited worldwide public health concerns, and mechanism regulating insulin secretion is unclear. We found that vascular endothelial growth factor B (VEGF-B) prevents MIN6 cells from secreting insulin through the PI3K-AKT (phosphatidylinositol 3-kinase-serine/threonine kinase) pathway. We have provided mechanistic insights into the effect of VEGF-B on insulin secretion and suggest VEGF-B as a new target that affects the occurrence and development of type 2 diabetes.