An insulin-like growth factor-II (IGF-II) analog with highly selective affinity for IGF-II receptors stimulates differentiation, but not IGF-I receptor down-regulation in muscle cells

Stephen M. Rosenthal, Don Hsiao, Lawrence Silverman

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37 Citations (Scopus)

Abstract

The insulin-like growth factors (IGFs) stimulate the growth and differentiation of muscle cells. IGF-II, the principal IGF peptide expressed by differentiating muscle cells, has been implicated in at least two autocrine/paracrine actions in this tissue: stimulation of differentiation and down-regulation of the IGF-I receptor. To determine which IGF receptor subtypes mediate these effects of IGF-II, we treated mouse BC3H-1 muscle cells with native IGF-II or [Leu27]IGF-II, an analog with high affinity for IGF-II receptors (comparable to that seen with native IGF-II) but markedly reduced affinity for IGF-I and insulin receptors. Muscle cell differentiation was assessed by the expression of myogenin mRNA and by the binding of α-bungarotoxin to the nicotinic acetylcholine receptor. IGF-I receptor down-regulation was assessed by receptor binding and mRNA abundance. Although less potent than IGF-II, the [Leu27]IGF-II analog stimulated myogenin gene expression and acetylcholine receptor binding in concentrations at which the analog interacted with IGF-II receptors, but not significantly with IGF-I receptors. In IGF-I receptor down-regulation studies, IGF-II pretreatment significantly decreased binding of IGF-I to the IGF-I receptor and decreased IGF-I receptor mRNA, whereas the IGF-II analog had only minimal effects. Thus, in addition to the IGF-I receptor which has been previously found to signal IGF-induced myogenesis, these results implicate a role for the IGF-II receptor in this process. In contrast, IGF-I receptor down-regulation induced by IGF-II is mediated through IGF-I, but not IGF-II, receptors in muscle cells.

Original languageEnglish (US)
Pages (from-to)38-44
Number of pages7
JournalEndocrinology
Volume135
Issue number1
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

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IGF Type 2 Receptor
IGF Type 1 Receptor
Insulin-Like Growth Factor II
Muscle Cells
Down-Regulation
Somatomedins
Myogenin
Insulin-Like Growth Factor I
Messenger RNA
Somatomedin Receptors
Bungarotoxins
Muscle Development
Insulin Receptor
Nicotinic Receptors
Cholinergic Receptors
Cell Differentiation

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

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title = "An insulin-like growth factor-II (IGF-II) analog with highly selective affinity for IGF-II receptors stimulates differentiation, but not IGF-I receptor down-regulation in muscle cells",
abstract = "The insulin-like growth factors (IGFs) stimulate the growth and differentiation of muscle cells. IGF-II, the principal IGF peptide expressed by differentiating muscle cells, has been implicated in at least two autocrine/paracrine actions in this tissue: stimulation of differentiation and down-regulation of the IGF-I receptor. To determine which IGF receptor subtypes mediate these effects of IGF-II, we treated mouse BC3H-1 muscle cells with native IGF-II or [Leu27]IGF-II, an analog with high affinity for IGF-II receptors (comparable to that seen with native IGF-II) but markedly reduced affinity for IGF-I and insulin receptors. Muscle cell differentiation was assessed by the expression of myogenin mRNA and by the binding of α-bungarotoxin to the nicotinic acetylcholine receptor. IGF-I receptor down-regulation was assessed by receptor binding and mRNA abundance. Although less potent than IGF-II, the [Leu27]IGF-II analog stimulated myogenin gene expression and acetylcholine receptor binding in concentrations at which the analog interacted with IGF-II receptors, but not significantly with IGF-I receptors. In IGF-I receptor down-regulation studies, IGF-II pretreatment significantly decreased binding of IGF-I to the IGF-I receptor and decreased IGF-I receptor mRNA, whereas the IGF-II analog had only minimal effects. Thus, in addition to the IGF-I receptor which has been previously found to signal IGF-induced myogenesis, these results implicate a role for the IGF-II receptor in this process. In contrast, IGF-I receptor down-regulation induced by IGF-II is mediated through IGF-I, but not IGF-II, receptors in muscle cells.",
author = "Rosenthal, {Stephen M.} and Don Hsiao and Lawrence Silverman",
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N2 - The insulin-like growth factors (IGFs) stimulate the growth and differentiation of muscle cells. IGF-II, the principal IGF peptide expressed by differentiating muscle cells, has been implicated in at least two autocrine/paracrine actions in this tissue: stimulation of differentiation and down-regulation of the IGF-I receptor. To determine which IGF receptor subtypes mediate these effects of IGF-II, we treated mouse BC3H-1 muscle cells with native IGF-II or [Leu27]IGF-II, an analog with high affinity for IGF-II receptors (comparable to that seen with native IGF-II) but markedly reduced affinity for IGF-I and insulin receptors. Muscle cell differentiation was assessed by the expression of myogenin mRNA and by the binding of α-bungarotoxin to the nicotinic acetylcholine receptor. IGF-I receptor down-regulation was assessed by receptor binding and mRNA abundance. Although less potent than IGF-II, the [Leu27]IGF-II analog stimulated myogenin gene expression and acetylcholine receptor binding in concentrations at which the analog interacted with IGF-II receptors, but not significantly with IGF-I receptors. In IGF-I receptor down-regulation studies, IGF-II pretreatment significantly decreased binding of IGF-I to the IGF-I receptor and decreased IGF-I receptor mRNA, whereas the IGF-II analog had only minimal effects. Thus, in addition to the IGF-I receptor which has been previously found to signal IGF-induced myogenesis, these results implicate a role for the IGF-II receptor in this process. In contrast, IGF-I receptor down-regulation induced by IGF-II is mediated through IGF-I, but not IGF-II, receptors in muscle cells.

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