Insulin and insulinlike growth factor receptors and responses in cultured human muscle cells

Specific receptors for insulinlike growth factors I and II (IGF-I and IGF-II) were found on cultured human myoblasts and myotubes. In contrast, myotubes but not myoblasts specifically bound insulin and were stimulated by nanomolar concentrations of insulin to take up deoxyglucose. In addition, in myoblasts, physiological concentrations of IGF-I and -II and, to a lesser extent, insulin stimulated two- to threefold the uptake of the nonmetabolizable amino acid analogue methylaminoisobutyric acid (MAIB). In myotubes, uptake of MAIB was stimulated preferentially by IGF-I. Monoclonal antibodies that preferentially recognize either the insulin receptor or the IGF-I receptor were utilized to examine which receptors mediated the biological effects of these hormones. The effects of insulin on both myoblasts and myotubes appeared to be mediated in part by the insulin receptor and in part by the IGF-I receptor. In myotubes, the effects of IGF-I and -II both appeared to be mediated through the IGF-I receptor. In myoblasts, the effects of the two IGFs appeared to be in part mediated by the IGF-I receptor and in part mediated by either the IGF-II receptor or another type of IGF-I receptor. The present results suggest that cultured human muscle cells provide a useful model system in which to study the biological actions of insulin and the IGFs.

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A novel isoform of myosin alkali light chain isolated from human muscle cells

Nucleic Acids Research ◽

10.1093/nar/17.24.10496 ◽

1989 ◽

Vol 17 (24) ◽

pp. 10496-10496 ◽

Cited By ~ 4

Author(s):

Katrin Zimmermann ◽

Anna Starzinski-Powitz

Keyword(s):

Light Chain ◽

Muscle Cells ◽

Human Muscle ◽

Human Muscle Cells

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Effects of Macrophage Conditioned-Medium on Murine and Human Muscle Cells: Analysis of Proliferation, Differentiation, and Fusion

Methods in Molecular Biology - Muscle Stem Cells ◽

10.1007/978-1-4939-6771-1_17 ◽

2017 ◽

pp. 317-327 ◽

Cited By ~ 6

Author(s):

Marielle Saclier ◽

Marine Theret ◽

Rémi Mounier ◽

Bénédicte Chazaud

Keyword(s):

Conditioned Medium ◽

Muscle Cells ◽

Human Muscle ◽

Human Muscle Cells

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Fibroblast growth factor 9 (FGF9) inhibits myogenic differentiation of C2C12 and human muscle cells

Cell Cycle ◽

10.1080/15384101.2019.1691796 ◽

2019 ◽

Vol 18 (24) ◽

pp. 3562-3580 ◽

Cited By ~ 5

Author(s):

Jian Huang ◽

Kun Wang ◽

Lora A. Shiflett ◽

Leticia Brotto ◽

Lynda F. Bonewald ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Myogenic Differentiation ◽

Muscle Cells ◽

Human Muscle ◽

Fibroblast Growth ◽

Human Muscle Cells

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Regulation of glycogen metabolism in cultured human muscles by the glycogen phosphorylase inhibitor CP-91149

Biochemical Journal ◽

10.1042/bj20030971 ◽

2004 ◽

Vol 378 (3) ◽

pp. 1073-1077 ◽

Cited By ~ 11

Author(s):

Carlos LERÍN ◽

Eulàlia MONTELL ◽

Teresa NOLASCO ◽

Mar GARCÍA-ROCHA ◽

Joan J. GUINOVART ◽

...

Keyword(s):

Muscle Glycogen ◽

Glycogen Phosphorylase ◽

Glycogen Synthase ◽

Muscle Cells ◽

Glycogen Metabolism ◽

Human Muscle ◽

Insulin Dependent Diabetes ◽

Type Ii ◽

Insulin Dependent ◽

Human Muscle Cells

Pharmacological inhibition of liver GP (glycogen phosphorylase), which is currently being studied as a treatment for Type II (non-insulin-dependent) diabetes, may affect muscle glycogen metabolism. In the present study, we analysed the effects of the GP inhibitor CP-91149 on non-engineered or GP-overexpressing cultured human muscle cells. We found that CP-91149 treatment decreased muscle GP activity by (1) converting the phosphorylated AMP-independent a form into the dephosphorylated AMP-dependent b form and (2) inhibiting GP a activity and AMP-mediated GP b activation. Dephosphorylation of GP was exerted, irrespective of incubation of the cells with glucose, whereas inhibition of its activity was synergic with glucose. As expected, CP-91149 impaired the glycogenolysis induced by glucose deprivation. CP-91149 also promoted the dephosphorylation and activation of GS (glycogen synthase) in non-engineered or GP-overexpressing cultured human muscle cells, but exclusively in glucose-deprived cells. However, this inhibitor did not activate GS in glucose-deprived but glycogen-replete cells overexpressing PTG (protein targeting to glycogen), thus suggesting that glycogen inhibits the CP-91149-mediated activation of GS. Consistently, CP-91149 promoted glycogen resynthesis, but not its overaccumulation. Hence, treatment with CP-91149 impairs muscle glycogen breakdown, but enhances its recovery, which may be useful for the treatment of Type II (insulin-dependent) diabetes.

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Developmental regulation of myotonic dystrophy protein kinase in human muscle cells in vitro

Neuroscience ◽

10.1016/s0306-4522(97)00602-7 ◽

1998 ◽

Vol 85 (1) ◽

pp. 311-322 ◽

Cited By ~ 8

Author(s):

N Kameda ◽

H Ueda ◽

S Ohno ◽

M Shimokawa ◽

F Usuki ◽

...

Keyword(s):

Protein Kinase ◽

Myotonic Dystrophy ◽

Developmental Regulation ◽

Muscle Cells ◽

Human Muscle ◽

Myotonic Dystrophy Protein Kinase ◽

Human Muscle Cells

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Differential Activation of Insulin Receptor Substrates 1 and 2 by Insulin-Like Growth Factor-Activated Insulin Receptors

Molecular and Cellular Biology ◽

10.1128/mcb.01447-06 ◽

2007 ◽

Vol 27 (10) ◽

pp. 3569-3577 ◽

Cited By ~ 63

Author(s):

Adam Denley ◽

Julie M. Carroll ◽

Gemma V. Brierley ◽

Leah Cosgrove ◽

John Wallace ◽

...

Keyword(s):

Growth Factor ◽

Insulin Receptor ◽

Splice Variants ◽

Biological Effects ◽

Insulin Receptors ◽

Insulin Like Growth Factor ◽

Extracellular Signal ◽

Igf I ◽

High Concentrations ◽

Kinase Pathway

ABSTRACT The insulin-like growth factors (insulin-like growth factor I [IGF-I] and IGF-II) exert important effects on growth, development, and differentiation through the IGF-I receptor (IGF-IR) transmembrane tyrosine kinase. The insulin receptor (IR) is structurally related to the IGF-IR, and at high concentrations, the IGFs can also activate the IR, in spite of their generally low affinity for the latter. Two mechanisms that facilitate cross talk between the IGF ligands and the IR at physiological concentrations have been described. The first of these is the existence of an alternatively spliced IR variant that exhibits high affinity for IGF-II as well as for insulin. A second phenomenon is the ability of hybrid receptors comprised of IGF-IR and IR hemireceptors to bind IGFs, but not insulin. To date, however, direct activation of an IR holoreceptor by IGF-I at physiological levels has not been demonstrated. We have now found that IGF-I can function through both splice variants of the IR, in spite of low affinity, to specifically activate IRS-2 to levels similar to those seen with equivalent concentrations of insulin or IGF-II. The specific activation of IRS-2 by IGF-I through the IR does not result in activation of the extracellular signal-regulated kinase pathway but does induce delayed low-level activation of the phosphatidylinositol 3-kinase pathway and biological effects such as enhanced cell viability and protection from apoptosis. These findings suggest that IGF-I can function directly through the IR and that the observed effects of IGF-I on insulin sensitivity may be the result of direct facilitation of insulin action by IGF-I costimulation of the IR in insulin target tissues.

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