title: Effects of insulin-like growth factor 1 on muscle atrophy and motor function in rats with brain ischemia.
abstract: Although insulin-like growth factor 1 (IGF 1) has been used in immobilizated muscles to prevent muscle atrophy, its effects on muscle atrophy after brain ischemia are not known. This study aimed to determine the effects of IGF 1 on preventing muscle atrophy in rats with brain ischemia. Middle cerebral artery occlusion (MCAO) was used to induce the brain ischemia. In the first part of the study, rats were assigned to sham control, ischemic control, and ischemia with different dosages of IGF 1 injection groups to determine the optimal dosage of IGF 1 on preventing muscle atrophy after brain ischemia. In the second part of the study, rats were assigned to sham control, ischemic control, ischemia with IGF 1, or with IGF 1 receptor inhibitor (AG1024) injection groups to determine the specificity of IGF 1 on preventing muscle atrophy after brain ischemia. IGF 1 or AG1024 was injected locally to calf muscles and anterior tibialis (TA) starting from one day after brain ischemia and injections were carried out every other day for 4 times. Muscle weight and myosin heavy chain (MHC) expression in both red (red gastrocnemius and soleus) and white (white gastrocnemius and TA) muscles were significantly decreased after brain ischemia. With at least moderate-dosage (200 ng/100 microl PBS) IGF 1 injection, the muscle weight and MHC protein could be restored in both red and white muscles resulting in better motor performance. However, the high-dose injection of IGF 1 (400 ng/100 microl PBS) did not result in further effects. IGF 1 increased the expression of p-Akt, but such effects were prevented by AG1024 resulting in muscle atrophy and poor motor function. In conclusion, peripheral application of IGF 1 not only prevented muscle atrophy but also enhanced motor function in rats with brain ischemia. The IGF 1-induced PI3K/Akt pathways are important for preventing muscle atrophy induced by brain ischemia.
authors.affiliation: Department and Institute of Physiology, National Yang-Ming University, Taiwan, Republic of China.
authors.forename: Heng-Chih
authors.initials: HC
authors.lastname: Chang
authors.forename: Yea-Ru
authors.initials: YR
authors.lastname: Yang
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Wang
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: Ray-Yau
authors.initials: RY
authors.lastname: Wang
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D002545:Brain Ischemia / Q000150:complications* / Q000209:etiology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009133:Muscular Atrophy / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D018995:Myosin Heavy Chains / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D020032:Tyrphostins; C447031:tyrphostin AG 1024; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D018995:Myosin Heavy Chains