Contents lists available at ScienceDirect Growth Hormone & IGF Research journal homepage: www.elsevier.com/locate/ghir Effect of amino acids on IGF1 gene expression in human myotubes and skeletal muscle Egor M. Lednev a, ⁎ , Irina V. Kravchenko b , Vladimir A. Furalyov b , Evgeny A. Lysenko a , Iulia S. Lemesheva a , Alexandr.A. Grushin c , Vadim E. Dubrov d , Olga L. Vinogradova a , Daniil V. Popov a a Institute of Biomedical Problems of the RAS, 76A Khoroshevskoye Shosse, Moscow 123007, Russian Federation b Federal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of Sciences, 33 build 2, Leninsky prospect, Moscow 119071, Russian Federation c Russian Olympic Committee, Luzhnetskaya Embankment 8, Russia, Moscow 119991, Russian Federation d Lomonosov Moscow State University, Faculty of Fundamental Medicine, 27 build. 1, Lomonosovsky Prospekt, Moscow 119991, Russian Federation ARTICLE INFO Keywords: IGF1 Amino acids Human myotubes Skeletal muscle Athletes Collagens Muscle damage Aerobic exercise training IGF1-dependent genes ABSTRACT Objective: Insulin-like growth factor I (IGF1) is an important regulator of collagen and extracellular matrix protein expression. We aimed to evaluate the effect of amino acids (AAs) on expression of IGF1 and IGF1- dependent genes in human myotubes and skeletal muscle and supposed that AAs administration increases IGF1 levels in blood and expression of IGF1 and IGF1-dependent genes in trained skeletal muscle, thereby reducing training-induced muscle damage. Design: Human myotubes were incubated with Arg and Leu for 24 h. Then, the effects of long-term branched chain AAs administration (10 weeks, 0.1 g/kg body mass/day) to volunteers (six subjects per AAs and placebo groups) performing large training volumes regularly (cross country skiers, training twice a day) were examined. Results: Incubating the myotubes with AAs increases expression of IGF1 mRNA isoforms and IGF1 secretion by 2–3 times. In athletes, long-term AAs administration increased basal blood levels of IGF1 (~50%) and expression of IGF1Ea mRNA slightly in skeletal muscle. There is no marked increase in expression of COL1A1, COL3A1, COL5A1, and LOX genes in skeletal muscle after AAs administration. However, expression of these genes in the combined group (placebo + AAs; n = 12) significantly correlated with the expression of IGF1Ea mRNA in muscle and did not correlate with IGF1 levels in the blood. Conclusions: AAs administration increases IGF1 expression in vitro and in vivo. To obtain more pronounced changes in expression of IGF1 and IGF1-dependent genes in skeletal muscle, it may be necessary to increase the dose and/or duration of AAs administration. 1. Introduction Muscle damage caused by intensive physical exercise may lead to edema, pain, and inflammation, thereby reducing functional capability [1]. This problem is relevant when people with impaired functional capabilities perform ordinary physical activity (for example, during rehabilitation after long-term bed rest), as well as for athletes who perform high intensity high volume exercises regularly. Damage to muscle membranes is one cause of delayed muscle soreness induced by physical activity. Increasing the stiffness of the cell membrane and extracellular matrix (ECM), which play a key role in the transfer of force to the sites of muscle attachment (endomysium and perimysium), can be effective at reducing exercise-induced damage of muscle fiber membranes and muscle soreness. Insulin-like growth factor I (IGF1) is an important regulator of collagen and ECM protein expression [2]. Research on cultured fetal mouse calvaria cells demonstrated that knockout of the Igf1 gene de- creased expression of collagens [3]. The same results were found in gut smooth muscle in chemically-induced mouse models of colitis: phar- macological inhibition of IGF1 receptor (IGF1R) phosphorylation [4] and knockdown of Igf1 [5] prevented an increase in Col1a1 expression, collagen synthesis, and fibrosis. By contrast, Igf1 overexpression in skeletal muscle of mdx mice (a model of Duchenne muscular dystrophy) restored the mechanical properties of tendons and reduced the number of necrotic cells within them [6]. Research involving volunteers and patients with acromegaly and growth hormone (GH) deficiency showed https://doi.org/10.1016/j.ghir.2020.101323 Received 20 January 2020; Received in revised form 11 April 2020 ⁎ Corresponding author. E-mail address: ledhauz@gmail.com (E.M. Lednev). Growth Hormone & IGF Research 53–54 (2020) 101323 Available online 28 April 2020 1096-6374/ © 2020 Elsevier Ltd. All rights reserved. T