PTEN Inhibition Improves Muscle Regeneration in Mice Fed a High-Fat Diet

• DOI: 10.2337/db09-1155
• Publication Date: 2010-03-04T02:56:03Z
• Authors: Zhaoyong Hu; Huiling Wang; In Hee Lee; Swati Modi; Xiaonan Wang; Jie Du; William E. Mitch
• Keywords: Knockout mouse

OBJECTIVE Mechanisms impairing wound healing in diabetes are poorly understood. To identify mechanisms, we induced insulin resistance by chronically feeding mice a high-fat diet (HFD). We also examined the regulation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) during muscle regeneration because augmented IGF-1 signaling can improve regeneration. RESEARCH DESIGN AND METHODS Muscle was cardiotoxin injury, and evaluated satellite cell activation maturation HFD-fed mice. measured PIP3 enzymes regulating its level, IRS-1–associated 3-kinase (PI3K) PTEN. Using primary cultures muscle, how fatty acids affect PTEN expression knockout influences growth. Mice with muscle-specific were used to examine HFD changes RESULTS The raised circulating impaired growth regenerating myofibers while delaying myofiber increasing collagen deposition. These independent proliferation progenitor or cells but principally related increased PTEN, which reduced muscle. In cultured cells, palmitate directly stimulated Knocking out restored mice, improved defects repair HFD. CONCLUSIONS Insulin impairs preventing maturation. mechanism involves acid–stimulated expression, lowers PIP3. If similar pathways occur diabetic patients, therapeutic strategies directed at improving damaged could include suppression activity.