PMID- 31969592
OWN - NLM
STAT- MEDLINE
DCOM- 20201130
LR  - 20210121
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Jan 22
TI  - VEGF-B ablation in pancreatic beta-cells upregulates insulin expression without 
      affecting glucose homeostasis or islet lipid uptake.
PG  - 923
LID - 10.1038/s41598-020-57599-2 [doi]
LID - 923
AB  - Type 2 diabetes mellitus (T2DM) affects millions of people and is linked with 
      obesity and lipid accumulation in peripheral tissues. Increased lipid handling 
      and lipotoxicity in insulin producing beta-cells may contribute to beta-cell 
      dysfunction in T2DM. The vascular endothelial growth factor (VEGF)-B regulates 
      uptake and transcytosis of long-chain fatty acids over the endothelium to tissues 
      such as heart and skeletal muscle. Systemic inhibition of VEGF-B signaling 
      prevents tissue lipid accumulation, improves insulin sensitivity and glucose 
      tolerance, as well as reduces pancreatic islet triglyceride content, under T2DM 
      conditions. To date, the role of local VEGF-B signaling in pancreatic islet 
      physiology and in the regulation of fatty acid trans-endothelial transport in 
      pancreatic islet is unknown. To address these questions, we have generated a 
      mouse strain where VEGF-B is selectively depleted in beta-cells, and assessed 
      glucose homeostasis, beta-cell function and islet lipid content under both normal 
      and high-fat diet feeding conditions. We found that Vegfb was ubiquitously 
      expressed throughout the pancreas, and that beta-cell Vegfb deletion resulted in 
      increased insulin gene expression. However, glucose homeostasis and islet lipid 
      uptake remained unaffected by beta-cell VEGF-B deficiency.
FAU - Ning, Frank Chenfei
AU  - Ning FC
AD  - Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, 
      Karolinska Institutet, Stockholm, 171 65, Sweden.
FAU - Jensen, Nina
AU  - Jensen N
AD  - Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, 
      Karolinska Institutet, Stockholm, 171 65, Sweden.
FAU - Mi, Jiarui
AU  - Mi J
AD  - Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, 
      Karolinska Institutet, Stockholm, 171 65, Sweden.
FAU - Lindstrom, William
AU  - Lindstrom W
AD  - Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, 
      Karolinska Institutet, Stockholm, 171 65, Sweden.
FAU - Balan, Mirela
AU  - Balan M
AD  - Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, 
      Karolinska Institutet, Stockholm, 171 65, Sweden.
FAU - Muhl, Lars
AU  - Muhl L
AD  - Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, 
      Karolinska Institutet, Stockholm, 171 65, Sweden.
FAU - Eriksson, Ulf
AU  - Eriksson U
AUID- ORCID: 0000-0002-4439-3980
AD  - Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, 
      Karolinska Institutet, Stockholm, 171 65, Sweden.
FAU - Nilsson, Ingrid
AU  - Nilsson I
AD  - Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, 
      Karolinska Institutet, Stockholm, 171 65, Sweden.
FAU - Nyqvist, Daniel
AU  - Nyqvist D
AUID- ORCID: 0000-0002-6527-6716
AD  - Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, 
      Karolinska Institutet, Stockholm, 171 65, Sweden. daniel.nyqvist@ki.se.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200122
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Fatty Acids)
RN  - 0 (Insulin)
RN  - 0 (Triglycerides)
RN  - 0 (Vascular Endothelial Growth Factor B)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Fatty Acids/*metabolism
MH  - *Gene Expression
MH  - Glucose/*metabolism
MH  - *Homeostasis
MH  - Insulin/*genetics/*metabolism
MH  - Insulin Resistance/genetics
MH  - Insulin-Secreting Cells/*metabolism
MH  - Mice, Transgenic
MH  - Signal Transduction/physiology
MH  - Triglycerides/metabolism
MH  - Up-Regulation/genetics
MH  - Vascular Endothelial Growth Factor B/*deficiency/metabolism/*physiology
PMC - PMC6976647
COIS- U.E. is a consultant to CSL Ltd. and is inventor on several patents describing 
      the role of VEGF-B in diabetes and diabetes complications. L.M., U.E., I.N. and 
      D.N. are shareholders in a company in the diabetes field.
EDAT- 2020/01/24 06:00
MHDA- 2020/12/01 06:00
PMCR- 2020/01/22
CRDT- 2020/01/24 06:00
PHST- 2019/09/29 00:00 [received]
PHST- 2019/12/18 00:00 [accepted]
PHST- 2020/01/24 06:00 [entrez]
PHST- 2020/01/24 06:00 [pubmed]
PHST- 2020/12/01 06:00 [medline]
PHST- 2020/01/22 00:00 [pmc-release]
AID - 10.1038/s41598-020-57599-2 [pii]
AID - 57599 [pii]
AID - 10.1038/s41598-020-57599-2 [doi]
PST - epublish
SO  - Sci Rep. 2020 Jan 22;10(1):923. doi: 10.1038/s41598-020-57599-2.