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Transendothelial Insulin Transport is Impaired in Skeletal Muscle Capillaries of
Obese Male Mice.
Authors Williams IM, McClatchey PM, Bracy DP, Bonner JS, Valenzuela FA, Wasserman DH
Submitted By Submitted Externally on 1/14/2020
Status Published
Journal Obesity (Silver Spring, Md.), References
Year 2020
Date Published 1/1/2020
Volume : Pages Not Specified : Not Specified
PubMed Reference 31903723
Abstract The continuous endothelium of skeletal muscle (SkM) capillaries regulates
insulin's access to skeletal myocytes. Whether impaired transendothelial insulin
transport (EIT) contributes to SkM insulin resistance (IR), however, is
unknown., Male and female C57/Bl6 mice were fed either chow or a high-fat diet
for 16 weeks. Intravital microscopy was used to measure EIT in SkM capillaries,
electron microscopy to assess endothelial ultrastructure, and glucose tracers to
measure indices of glucose metabolism., Diet-induced obesity (DIO) male mice
were found to have a ~15% reduction in EIT compared with lean mice. Impaired EIT
was associated with a 45% reduction in endothelial vesicles. Despite impaired
EIT, hyperinsulinemia sustained delivery of insulin to the interstitial space in
DIO male mice. Even with sustained interstitial insulin delivery, DIO male mice
still showed SkM IR indicating severe myocellular IR in this model.
Interestingly, there was no difference in EIT, endothelial ultrastructure, or
SkM insulin sensitivity between lean female mice and female mice fed a high-fat
diet., These results suggest that, in male mice, obesity results in
ultrastructural alterations to the capillary endothelium that delay EIT.
Nonetheless, the myocyte appears to exceed the endothelium as a contributor to
SkM IR in DIO male mice.


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