Insulin and IGF-I induce pronounced hypertrophy of skeletal myofibers in tissue culture.
Skeletal myofibers differentiated from primary avian myoblasts in tissue culture can be maintained in positive nitrogen balance in a defined serum-free medium for at least 6-7 days when embedded in a three-dimensional collagen gel matrix. Incubation of established myofiber cultures for 3-7 days with insulin (1 microM) or insulin-like growth factor I (IGF-I, 32 nM) stimulates both cell hyperplasia and myofiber hypertrophy. Mean myofiber diameter increases 71-98%. Insulin-like growth factor II stimulates cell hyperplasia but not myofiber hypertrophy. Cell growth results from a 42-62% increase in total protein synthesis and a 28-38% decrease in protein degradation. Myosin heavy-chain content increases 183-258% because of a 55% stimulation of myosin synthesis and 33-61% inhibition of degradation. Associated with myofiber hypertrophy is a 87-148% increase in the number of myofiber nuclei per unit myofiber length. The results indicate that insulin and IGF-I, but not IGF-II, can induce rapid myofiber hypertrophy in vitro, most likely by stimulating myoblast proliferation and/or fusion to established myofibers.
Vandenburgh
H H
HH
Department of Pathology, Brown University, Providence, Rhode Island 02906.
Karlisch
P
P
Shansky
J
J
Feldstein
R
R
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D006984:Hypertrophy; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D007700:Kinetics; D009132:Muscles / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D009210:Myofibrils / Q000187:drug effects / Q000648:ultrastructure; D010649:Phenylalanine / Q000378:metabolism; D014176:Protein Biosynthesis
D007328:Insulin; D010649:Phenylalanine; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II