Interaction of insulin-like growth factors with a nonfusing mouse muscle cell line: binding, action, and receptor down-regulation. 1984

M A de Vroede, and J A Romanus, and M L Standaert, and R J Pollet, and S P Nissley, and M M Rechler

Insulin and the insulin-like growth factors (IGFs) are chemically related polypeptides that interact with distinct receptors and elicit the same biological responses. We have sought a readily propagated cell line from a potential target tissue in which to probe the multiple and complex interrelationships among receptor and effector pathways for these polypeptides. We now report that the mouse muscle cell line BC3H-1 represents such a model system. BC3H-1 cells differentiate spontaneously at high density to form cells with muscle-specific properties, but do not fuse. Standaert et al. reported that differentiated BC3H-1 myocytes possess insulin receptors that mediate glucose and amino acid uptake and are down-regulated by prolonged incubation with insulin. The present report demonstrates that BC3H-1 myocytes also possess functional and regulated IGF receptors. Two subtypes of IGF receptors, types I and II, differing in structure and peptide specificity, were demonstrated by competitive binding and affinity cross-linking experiments. Low concentrations of IGFs stimulated glucose incorporation and alpha-aminoisobutyric acid uptake by BC3H-1 myocytes, suggesting that these effects were mediated primarily by IGF receptors rather than insulin receptors. Preincubation with IGFs (or high concentrations of insulin) selectively down-regulated type I IGF receptors without affecting type II IGF receptors. Since [125I]IGF-I binds to both type I and type II receptors in BC3H-1 cells, and since type I receptors have a higher affinity for IGF-I, the selective down-regulation of type I IGF receptors results in an apparent decrease in affinity for IGF-I. This difference in the regulation of type I and type II receptors in BC3H-1 myocytes is consistent with observations in other systems in which only one IGF receptor was present or examined. In their ability to be down-regulated by IGFs and insulin, type I IGF receptors are more similar to the structurally homologous insulin receptors than to the structurally dissimilar type II IGF receptors. These findings indicate that the BC3H-1 cell line provides an excellent model system in which to study the structure-function relationships of the receptor and effector pathways for insulin and the IGFs.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D000596 Amino Acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Amino Acid,Acid, Amino,Acids, Amino
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013002 Somatomedins Insulin-like polypeptides made by the liver and some fibroblasts and released into the blood when stimulated by SOMATOTROPIN. They cause sulfate incorporation into collagen, RNA, and DNA synthesis, which are prerequisites to cell division and growth of the organism. Sulfation Factor,Somatomedin,Factor, Sulfation
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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