VEGF-B ablation in pancreatic β-cells upregulates insulin expression without affecting glucose homeostasis or islet lipid uptake.
Animals
Diabetes Mellitus, Type 2
/ metabolism
Fatty Acids
/ metabolism
Gene Expression
Glucose
/ metabolism
Homeostasis
Insulin
/ genetics
Insulin Resistance
/ genetics
Insulin-Secreting Cells
/ metabolism
Mice, Transgenic
Signal Transduction
/ physiology
Triglycerides
/ metabolism
Up-Regulation
/ genetics
Vascular Endothelial Growth Factor B
/ deficiency
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 01 2020
22 01 2020
Historique:
received:
29
09
2019
accepted:
18
12
2019
entrez:
24
1
2020
pubmed:
24
1
2020
medline:
1
12
2020
Statut:
epublish
Résumé
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 β-cells may contribute to β-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 β-cells, and assessed glucose homeostasis, β-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 β-cell Vegfb deletion resulted in increased insulin gene expression. However, glucose homeostasis and islet lipid uptake remained unaffected by β-cell VEGF-B deficiency.
Identifiants
pubmed: 31969592
doi: 10.1038/s41598-020-57599-2
pii: 10.1038/s41598-020-57599-2
pmc: PMC6976647
doi:
Substances chimiques
Fatty Acids
0
Insulin
0
Triglycerides
0
Vascular Endothelial Growth Factor B
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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