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Publication
Muscle-specific vascular endothelial growth factor deletion induces muscle
capillary rarefaction creating muscle insulin resistance
Authors Bonner JS, Lantier L, Hasenour CM, James FD, Bracy DP, Wasserman DH
Submitted By Fran Tripp on 3/5/2013
Status In press
Journal Diabetes
Year 2012
Date Published 9/21/2013
Volume : Pages 62 : 572 - 580
PubMed Reference 23002035
Abstract Muscle insulin resistance is associated with a reduction in vascular endothelial
growth factor (VEGF) action and muscle capillary density. We tested the
hypothesis that muscle capillary rarefaction critically contributes to the
etiology of muscle insulin resistance in chow-fed mice with skeletal and cardiac
muscle VEGF deletion (mVEGF(-/-)) and wild-type littermates (mVEGF(+/+)) on a
C57BL/6 background. The mVEGF(-/-) mice had an ~60% and ~50% decrease in
capillaries in skeletal and cardiac muscle, respectively. The mVEGF(-/-) mice
had augmented fasting glucose turnover. Insulin-stimulated whole-body glucose
disappearance was blunted in mVEGF(-/-) mice. The reduced peripheral glucose
utilization during insulin stimulation was due to diminished in vivo cardiac and
skeletal muscle insulin action and signaling. The decreased insulin-stimulated
muscle glucose uptake was independent of defects in insulin action at the
myocyte, suggesting that the impairment in insulin-stimulated muscle glucose
uptake was due to poor muscle perfusion. The deletion of VEGF in cardiac muscle
did not affect cardiac output. These studies emphasize the importance for novel
therapeutic approaches that target the vasculature in the treatment of
insulin-resistant muscle




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