Insulin and insulin-like growth factor I regulate the same biological functions in HEP-G2 cells via their own specific receptors.
The receptors for insulin and insulin-like growth factor I (IGF-I) are closely related molecules, with an extracellular binding domain and an intracellular tyrosine kinase domain. The interaction of insulin and IGF-I with their respective receptors activates the receptor kinase domain, leading to the biological actions of the hormones. Since insulin generally regulates metabolic events and IGF-I generally regulates growth events, it is believed that structural differences in the tyrosine kinase domains of the two respective receptors may elicit different biological responses via different transmembrane signaling mechanisms. We studied the regulation of glycogen metabolism and amino acid uptake in human cultured HEP-G2 hepatoma cells, which have distinct receptors for both insulin and IGF-I. The receptor specificity of these responses was probed with specific monoclonal antibodies to both the insulin and IGF-I receptors. Stimulation of both [3H]glucose incorporation into glycogen and alpha-[3H]aminoisobutyric acid uptake by insulin was half-maximal at concentrations of 1-5 nmol/L. These effects were blocked by the insulin receptor monoclonal antibody MA-10, but not by the IGF-I receptor antibody alpha IR-3. Stimulation of both functions by IGF-I was half-maximal at concentrations of 1-5 nmol/L, and these effects were inhibited by alpha IR-3, but not by MA-10. These studies indicate that in HEP-G2 cells both insulin and IGF-I, via their own receptors, stimulate the same biological responses.
Verspohl
E J
EJ
Cell Biology Laboratory, Mount Zion Hospital and Medical Center, San Francisco, California 94120.
Maddux
B A
BA
Goldfine
I D
ID
D000596:Amino Acids / Q000378:metabolism; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D011972:Receptor, Insulin / Q000032:analysis / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D000911:Antibodies, Monoclonal; D007328:Insulin; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D006003:Glycogen; D011972:Receptor, Insulin; D005947:Glucose