1. COMP-angiopoietin-1 enhances skeletal muscle blood flow and insulin sensitivity in mice
- Author
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Hoon-Ki, Sung, H K, Sung, Yong-Woon, Kim, Soo Jeong, Choi, Jong-Yeon, Kim, Kyung Hee, Jeune, Kyu-Chang, Won, Jason K, Kim, Gou Young, Koh, Gyu Young, Koh, and So-Young, Park
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Physiology ,Recombinant Fusion Proteins ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Glucose uptake ,Biology ,Mice ,Gastrocnemius muscle ,chemistry.chemical_compound ,Insulin resistance ,Physiology (medical) ,Internal medicine ,medicine ,Hyperinsulinemia ,Animals ,Humans ,Insulin ,Glycolysis ,Phosphorylation ,Muscle, Skeletal ,Cells, Cultured ,Glycogen ,Skeletal muscle ,Articles ,medicine.disease ,Dietary Fats ,Mice, Inbred C57BL ,Oncogene Protein v-akt ,medicine.anatomical_structure ,Endocrinology ,Liver ,chemistry ,Regional Blood Flow ,Body Composition ,Diet, Atherogenic ,Insulin Resistance - Abstract
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.
- Published
- 2009