PMID- 37681454
OWN - NLM
STAT- MEDLINE
DCOM- 20230911
LR  - 20230922
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 28
IP  - 4
DP  - 2023 Oct
TI  - Vascular endothelial growth factor B regulates insulin secretion in beta cells of 
      type 2 diabetes mellitus mice via PLCgamma and the IP3R‑evoked Ca2(+)/CaMK2 signaling 
      pathway.
LID - 197 [pii]
LID - 10.3892/mmr.2023.13084 [doi]
AB  - Vascular endothelial growth factor B (VEGFB) plays a crucial role in glucolipid 
      metabolism and is highly associated with type 2 diabetes mellitus (T2DM). The 
      role of VEGFB in the insulin secretion of beta cells remains unverified. Thus, the 
      present study aimed to discuss the effect of VEGFB on regulating insulin 
      secretion in T2DM development, and its underlying mechanism. A high‑fat diet and 
      streptozocin (STZ) were used for inducing T2DM in mice model, and VEGFB gene in 
      islet cells of T2DM mice was knocked out by CRISPR Cas9 and overexpressed by 
      adeno‑Associated Virus (AAV) injection. The effect of VEGFB and its underlying 
      mechanism was assessed by light microscopy, electron microscopy and fluorescence 
      confocal microscopy, enzyme‑linked immunosorbent assay, mass spectrometer and 
      western blot analysis. The decrement of insulin secretion in islet beta cell of T2DM 
      mice were aggravated and blood glucose remained at a high level after VEGFB 
      knockout (KO). However, glucose tolerance and insulin sensitivity of T2DM mice 
      were improved after the AAV‑VEGFB(186) injection. VEGFB KO or overexpression can 
      inhibit or activate PLCgamma/IP3R in a VEGFR1‑dependent manner. Then, the change of 
      PLCgamma/IP3R caused by VEGFB/VEGFR1 will alter the expression of key factors on the 
      Ca2(+)/CaMK2 signaling pathway such as PPP3CA. Moreover, VEGFB can cause altered 
      insulin secretion by changing the calcium concentration in beta cells of T2DM mice. 
      These findings indicated that VEGFB activated the Ca2(+)/CaMK2 pathway via 
      VEGFR1‑PLCgamma and IP3R pathway to regulate insulin secretion, which provides new 
      insight into the regulatory mechanism of abnormal insulin secretion in T2DM.
FAU - Li, Yuqi
AU  - Li Y
AD  - Department of Pathophysiology, School of Basic Medicine of Binzhou Medical 
      University, Yantai, Shandong 264000, P.R. China.
FAU - Li, Rongrong
AU  - Li R
AD  - Department of Pathophysiology, School of Basic Medicine of Binzhou Medical 
      University, Yantai, Shandong 264000, P.R. China.
FAU - Luo, Xu
AU  - Luo X
AD  - Department of Pathophysiology, School of Basic Medicine of Binzhou Medical 
      University, Yantai, Shandong 264000, P.R. China.
FAU - Xu, Fang
AU  - Xu F
AD  - Department of Pathophysiology, School of Basic Medicine of Binzhou Medical 
      University, Yantai, Shandong 264000, P.R. China.
FAU - Yang, Meizi
AU  - Yang M
AD  - Department of Pharmacology, School of Basic Medicine of Binzhou Medical 
      University, Yantai, Shandong 264000, P.R. China.
FAU - Zheng, Lanhui
AU  - Zheng L
AD  - The First School of Clinical Medicine, Binzhou Medical University, Yantai, 
      Shandong 264000, P.R. China.
FAU - Wu, Qihao
AU  - Wu Q
AD  - The First School of Clinical Medicine, Binzhou Medical University, Yantai, 
      Shandong 264000, P.R. China.
FAU - Jiang, Wenguo
AU  - Jiang W
AD  - Department of Pharmacy, Binzhou Medical University, Yantai, Shandong 264000, P.R. 
      China.
FAU - Li, Yana
AU  - Li Y
AD  - Department of Pathophysiology, School of Basic Medicine of Binzhou Medical 
      University, Yantai, Shandong 264000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20230908
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Vascular Endothelial Growth Factor B)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Insulin Secretion
MH  - *Diabetes Mellitus, Type 2
MH  - Vascular Endothelial Growth Factor B
MH  - *Insulin-Secreting Cells
MH  - Signal Transduction
MH  - *Craniocerebral Trauma
MH  - Dependovirus/genetics
PMC - PMC10510031
OTO - NOTNLM
OT  - Ca2+/CaMK2
OT  - PLCgamma/IP3R
OT  - VEGFB
OT  - insulin secretion
OT  - type 2 diabetes mellitus
OT  - beta cell
COIS- The authors declare that they have no competing interests.
EDAT- 2023/09/08 12:42
MHDA- 2023/09/11 06:43
PMCR- 2023/09/05
CRDT- 2023/09/08 06:41
PHST- 2023/03/01 00:00 [received]
PHST- 2023/08/09 00:00 [accepted]
PHST- 2023/09/11 06:43 [medline]
PHST- 2023/09/08 12:42 [pubmed]
PHST- 2023/09/08 06:41 [entrez]
PHST- 2023/09/05 00:00 [pmc-release]
AID - 197 [pii]
AID - MMR-28-4-13084 [pii]
AID - 10.3892/mmr.2023.13084 [doi]
PST - ppublish
SO  - Mol Med Rep. 2023 Oct;28(4):197. doi: 10.3892/mmr.2023.13084. Epub 2023 Sep 8.