COMP-angiopoietin-1 enhances skeletal muscle blood flow and insulin sensitivity in mice

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Sung HK, Kim YW, Choi SJ, Kim JY, Jeune KH, Won KC, Kim JK, Koh GY, Park SY. COMP-angiopoietin-1 enhances skeletal muscle blood flow and insulin sensitivity in mice. Am J Physiol Endocrinol Metab 297: E402-E409, 2009. First published June 2, 2009; doi: 10.1152/ajpendo.00122.2009.-To test whether chronic enhanced blood flow alters insulin-stimulated glucose uptake, we measured skeletal muscle glucose uptake in chow-fed and high-fat-fed mice injected with adenovirus containing modified angiopoietin-1, COMP-Ang1, via euglycemic-hyperinsulinemic clamp. Blood flow rates and platelet endothelial cell adhesion molecule-1 positive endothelial cells in the hindlimb skeletal muscle were elevated in COMP-Ang1 compared with control LacZ. Whole body glucose uptake and whole body glycogen/lipid synthesis were elevated in COMP-Ang1 compared with LacZ in chow diet. High-fat diet significantly reduced whole body glucose uptake and whole body glycolysis in LacZ mice, whereas high-fat-fed COMP-Ang1 showed a level of whole body glucose uptake that was comparable with chow-fed LacZ and showed increased glucose uptake compared with high-fat-fed LacZ. Glucose uptake and glycolysis in gastrocnemius muscle of chow-fed COMP-Ang1 were increased compared with chow-fed LacZ. High-fat diet-induced whole body insulin resistance in the LacZ was mostly due to similar to 40% decrease in insulin-stimulated glucose uptake in skeletal muscle. In contrast, COMP-Ang1 prevented diet-induced skeletal muscle insulin resistance compared with high-fat-fed LacZ. Akt phosphorylation in skeletal muscle was increased in COMP-Ang1 compared with LacZ in both chow-fed and high-fat-fed groups. These results suggest that increased blood flow by COMP-Ang1 increases insulin-stimulated glucose uptake and prevents high-fat diet-induced insulin resistance in skeletal muscle.
Publisher
AMER PHYSIOLOGICAL SOC
Issue Date
2009-08
Language
English
Article Type
Article
Keywords

MEDIATED CAPILLARY RECRUITMENT; GLUCOSE-UPTAKE; OVEREXPRESSING ANGIOPOIETIN-1; TIE2 RECEPTOR; HIGH-FAT; IN-VIVO; RESISTANCE; DYSFUNCTION; EXPRESSION; VASCULARIZATION

Citation

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v.297, pp.E402 - E409

ISSN
0193-1849
DOI
10.1152/ajpendo.00122.2009
URI
http://hdl.handle.net/10203/101291
Appears in Collection
MSE-Journal Papers(저널논문)
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