Metabolic and mitogenic effects of IGF-I and insulin on muscle cells of rainbow trout

Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal 645, E-08028 Barcelona, Spain.
AJP Regulatory Integrative and Comparative Physiology (Impact Factor: 3.11). 06/2004; 286(5):R935-41. DOI: 10.1152/ajpregu.00459.2003
Source: PubMed


The relative function of IGF-I and insulin on fish muscle metabolism and growth has been investigated by the isolation and culture at different stages (myoblasts at day 1, myocytes at day 4, and myotubes at day 10) of rainbow trout muscle cells. This in vitro model avoids interactions with endogenous peptides, which could interfere with the muscle response. In these cells, the effects of IGF-I and insulin on cell proliferation, 2-deoxyglucose (2-DG), and l-alanine uptake at different development stages, and the use of inhibitors were studied and quantified. Insulin (10-1,000 nM) and IGF-I (10-100 nM) stimulated 2-DG uptake in trout myocytes at day 4 in a similar manner (maximum of 124% for insulin and of 142% for IGF-I), and this stimulation increased when cells differentiated to myotubes (maximum for IGF-I of 193%). When incubating the cells with PD-98059 and especially cytochalasin B, a reduction in 2-DG uptake was observed, suggesting that glucose transport takes place through specific facilitative transporters. IGF-I (1-100 nM) stimulated the l-alanine uptake in myocytes at day 4 (maximum of 239%), reaching higher values of stimulation than insulin (100-1,000 nM) (maximum of 160%). This stimulation decreased when cells developed to myotubes at day 10 (118% for IGF-I and 114% for insulin). IGF-I (0.125-25 nM) had a significant effect on myoblast proliferation, measured by thymidine incorporation (maximum of 170%), and required the presence of 2-5% fetal serum (FBS) to promote thymidine uptake. On the other hand, insulin was totally ineffective in stimulating thymidine uptake. We conclude that IGF-I is more effective than insulin in stimulating glucose and alanine uptake in rainbow trout myosatellite cells and that the degree of stimulation changes when cells differentiate to myotubes. IGF-I stimulates cell proliferation in this model of muscle in vitro and insulin does not. These results indicate the important role of IGF-I on growth and metabolism of fish muscle.

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Available from: M. L. Martínez, Dec 23, 2014
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    • "Furthermore, fish liver is a principal site of detoxification, lipid synthesis, and deposition , related to energy homeostasis. Environmental stress could affect the expression of key hepatic genes involved in lipid and energy metabolic regulation, such as fatty acid synthase (FAS) and growth hormone receptor/insulin-like growth factors (GHR/IGF) axis [13] [14]. Many of these effects are reported to be caused by interference with receptors regulating cellular signalling pathways, such as peroxisome proliferator-activated receptors (PPARs), and sterol-regulator element-binding protein-1 (SREBP-1) [15] [16]. "
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    • "Insulin also stimulates lipoprotein lipase (LPL) activity in rainbow trout adipose tissue [17] and reduces the basal lipolysis level in rainbow trout and gilthead sea bream adipocytes [7] [8]. Insulin-like growth factor (IGF)-I is structurally and functionally similar to insulin but is more potent as a growth factor and a metabolic controller in rainbow trout and gilthead sea bream myocytes and adipocytes [10] [14] [15] [18]. In vertebrates, many of the growth-promoting actions of GH are known to be mediated indirectly through the stimulation of IGF transcription, mainly by the liver, or locally by extra hepatic tissues [19], but the mechanisms of action involved in GH proliferative and metabolic effects in fish are not well known [20]. "
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    ABSTRACT: The aim of this study was to determine the effects of growth hormone (GH) and insulin-like growth factor (IGF)-I on glycerol release and the regulation of IGF-I and IGF-II expression by GH in isolated rainbow trout adipocytes. Cells were also incubated with GH, tumor necrosis factor α (TNFα), or insulin to analyze the gene expression of peroxisome proliferator-activated receptors (PPARs) and lipid metabolism markers: hormone sensitive lipase, fatty acid synthase (FAS), and lipoprotein lipase. Complimentary in vivo experiments were performed by intraperitoneally administering insulin, TNFα, or lipopolysaccharide and subjecting the animals to fasting and refeeding periods. The results showed that IGF-I had an antilipolytic effect and GH had a lipolytic effect; the latter occurred independently of IGF modulation and in conjunction with a reduction in PPARα expression in adipocytes. The anabolic action of insulin was demonstrated through its upregulation of lipogenic genes such as lipoprotein lipase, FAS, and PPARγ, whereas GH, by contrast, inhibited FAS expression in adipose tissue. The gene transcription levels of PPARs changed differentially during fasting and refeeding, and the TNFα and/or lipopolysaccharide administration suggested that the regulation of PPARs helps maintain metabolic adipose tissue homeostasis in rainbow trout.
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    • "In contrast, the expression for both paralogues of igf2 did not change significantly (Fig. 2C, D). IGFs have dramatic and direct effects on fish muscle growth by stimulating glucose and amino acid uptake, protein synthesis, and myoblast proliferation (Castillo et al., 2004; Codina et al., 2008; Garikipati and Rodgers, 2012a,b; Montserrat et al., 2012). Interestingly, igf2 is much more expressed than igf1 in the skeletal muscle of various fish species (Fuentes et al., 2013b), and IGF2 has stronger effects than IGF1 on myocyte proliferation (Rius-Francino et al., 2011). "
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