Muscle IGF-1-Induced Skeletal Muscle Hypertrophy Evokes Higher Insulin Sensitivity and Carbohydrate Use as Preferential Energy Substrate

作者:Christoffolete Marcelo Augusto; Silva William Jose; Ramos Gracielle Vieira; Bento Mirella Ribeiro; Costa Monique Oliveira; Ribeiro Miriam Oliveira; Okamoto Maristela Mitiko; Lohmann Tania Helena; Machado Ubiratan Fabres; Musaro Antonio; Moriscot Anselmo Sigari*
来源:Biomed Research International, 2015, 2015: 282984.
DOI:10.1155/2015/282984

摘要

We characterized the metabolic profile of transgenic mice exhibiting enhanced muscle mass driven by increased mIGF-1 expression (MLC/mIGF-1). As expected, 6-month-old MLC/mIGF-1 mice were heavier than age-matched wild type (WT) mice (37.4 +/- 0.3 versus 31.8 +/- 0.6 g, resp.). MLC/mIGF-1 mice had higher respiratory quotient when compared to WT (0.9 +/- 0.03 versus 0.74 +/- 0.02, resp.) suggesting a preference for carbohydrate as the major fuel source. MLC/mIGF-1 mice had a higher rate of glucose disposal when compared to WT (3.25 +/- 0.14 versus 2.39 +/- 0.03%/min, resp.). The higher disposal rate correlated to similar to 2-fold higher GLUT4 content in the extensor digitorum longus (EDL) muscle. Analysis of mRNA content for the glycolysis-related gene PFK-1 showed similar to 3-fold upregulation in MLC/mIGF-1 animals. We also found a 50% downregulation of PGC1 alpha mRNA levels in MLC/mIGF-1 mouse EDL muscle, suggesting less abundant mitochondria in this tissue. We found no difference in the expression of PPAR alpha and PPAR beta/delta, suggesting no modulation of key elements in oxidative metabolism. These data together suggest a shift in metabolism towards higher carbohydrate utilization, and that could explain the increased insulin sensitivity of hypertrophied skeletal muscle in MLC/mIGF-1 mice.

  • 出版日期2015