Metabolic and mitogenic effects of IGF-II in rainbow trout (Oncorhynchus mykiss) myocytes in culture and the role of IGF-II in the PI3K/Akt and MAPK signalling pathways.
Primary cultures of rainbow trout skeletal muscle cells were used to examine the role of insulin-like growth factor II (IGF-II) in fish muscle metabolism and growth, and to compare its main signal transduction pathways with those of IGF-I. IGF-II stimulated 2-deoxy-d-glucose (2-DG) uptake in trout myocytes at concentrations of between 5 and 100 nM, with similar maximal effects and temporal pattern to IGF-I (100 nM). The results of incubation with inhibitors (Wortmannin and CKB) indicated that IGF-II stimulates glucose uptake through the same mechanisms as IGF-I. In addition, IGF-II stimulated myoblast DNA synthesis (measured by thymidine incorporation) at relatively low concentrations (0.1-10 nM), with the maximum increase at 1 nM (167+/-17% with respect to control values). The cells were immunoreactive against ERK 1/2 MAPK and Akt/PKB, components of the two main signal transduction pathways for the IGF-I receptor. IGF-II stimulated the phosphorylation of the protein MAPK, especially at the proliferation stage (increases of up to 125.7+/-16.9% and 125.3+/-3.3% with respect to control in IGF-II- and IGF-I-treated cells, respectively). In contrast, the effects of both IGFs on the activation of the PI3K/Akt pathway were stronger in fully differentiated myocytes and in early-formed fibres (up to 359+/-18.5% in IGF-II-treated cells with respect to control). These results indicate that IGF-II has both mitogenic and metabolic effects in trout muscle cells, which are equivalent to those found in response to IGF-I. Both IGFs exert these effects though the same signalling pathways (MAPK and PI3K/Akt).
Codina
Marta
M
Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, España. Av. Diagonal 645, E-08028 Barcelona, Spain.
García de la serrana
Daniel
D
Sánchez-Gurmaches
Joan
J
Montserrat
Núria
N
Chistyakova
Oxana
O
Navarro
Isabel
I
Gutiérrez
Joaquim
J
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017686:Oncorhynchus mykiss; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases