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The effects of metformin on age-related changes in the liver sinusoidal endothelial cell

Permanent link
https://hdl.handle.net/10037/17754
DOI
https://doi.org/10.1093/gerona/glz153
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Date
2019-06-14
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Author
Hunt, Nick; Lockwood, Glen P; Kang, Sun; Pulpitel, Tamara; Clark, Ximonie; Mao, Hong; McCourt, Peter Anthony; Cooney, Greg; Wali, Jibran; Le Couteur, Frank; Le Couteur, David George; Cogger, Victoria Carroll
Abstract
Age-related changes in the liver sinusoidal endothelium, particularly the reduction in fenestrations, contribute to insulin resistance in old age. Metformin impacts on the aging process and improves insulin resistance. Therefore, the effects of metformin on the liver sinusoidal endothelium were studied. Metformin increased fenestrations in liver sinusoidal endothelial cells isolated from both young and old mice. Mice administered metformin in the diet for 12 months had increased fenestrations and this was associated with lower insulin levels. The effect of metformin on fenestrations was blocked by inhibitors of AMP-activated protein kinase (AMPK), endothelial nitric oxide synthase, and myosin light chain kinase phosphorylation. Metformin led to increased transgelin expression and structural changes in the actin cytoskeleton but had no effect on lactate production. Metformin also generated fenestration-like structures in SK-Hep1 cells, a liver endothelial cell line, and this was associated with increased ATP, cGMP, and mitochondrial activity. In conclusion, metformin ameliorates age-related changes in the liver sinusoidal endothelial cell via AMPK and endothelial nitric oxide pathways, which might promote insulin sensitivity in the liver, particularly in old age.
Publisher
Oxford University Press
Citation
Hunt, Lockwood GP, Kang, Pupitel, Clark, Mao H, McCourt PAG, Cooney, Wali, Le Couteur, Le Couteur DG, Cogger VC. The effects of metformin on age-related changes in the liver sinusoidal endothelial cell. The journals of gerontology. Series A, Biological sciences and medical sciences. 2019
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  • Artikler, rapporter og annet (medisinsk biologi) [1103]
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