COMP-angiopoietin-1 enhances skeletal muscle blood flow and insulin sensitivity in mice.
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 approximately 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.
Sung
Hoon-Ki
HK
Department of Biological Science, Korea Advanced Institute of Science and Technology, Biomedical Research Center, Daejeon, South Korea.
Sung
H K
HK
Kim
Yong-Woon
YW
Choi
Soo Jeong
SJ
Kim
Jong-Yeon
JY
Jeune
Kyung Hee
KH
Won
Kyu-Chang
KC
Kim
Jason K
JK
Koh
Gou Young
GY
Koh
Gyu Young
GY
Park
So-Young
SY
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D002478:Cells, Cultured; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects*
D001786:Blood Glucose; C515576:COMP-Ang1 fusion protein; D004041:Dietary Fats; D007328:Insulin; D011993:Recombinant Fusion Proteins; D051058:Oncogene Protein v-akt