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This Article Full Text Full Text (PDF) A corrigendum has been published All Versions of this Article: 297/2/E402    most recent 00122.2009v2 00122.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Google Scholar Articles by Sung, H. K. Articles by Park, S.-Y. PubMed PubMed Citation Articles by Sung, H. K. Articles by Park, S.-Y.

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

¹Biomedical Research Center and Department of Biological Science, Korea Advanced Institute of Science and Technology, Daejeon; ²Department of Physiology, College of Medicine, Yeungnam University, Daegu; ³Department of Biology, College of Science, Yeungnam University, Gyeongsan; ⁴Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, South Korea; ⁵Division of Endocrinology, Metabolism and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts; and ⁶Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu, South Korea

Submitted 24 February 2009 ; accepted in final form 27 May 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 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.

glucose uptake; high-fat diet; hyperinsulinemic-euglycemic clamp