Neonatal rat islet cell cultures synthesize insulin-like growth factor I.
Monolayer cultures of islet B-cells were established from neonatal rat pancreas. Serum-free media conditioned by these cultures for 72 h were concentrated and fractionated on Sephadex G-50 at acid pH into a high-molecular-weight pool containing binding protein for insulin-like growth factors (IGFs) and a low-molecular-weight pool containing IGFs. IGF activity in the IGF pool was demonstrated by a specific radioreceptor assay using rat liver plasma membranes and 125I-labeled rat IGF-II. The IGF in islet cell media was characterized further by radioimmunoassays specific for human IGF-I and for rat IGF-II. Islet cell IGF was identified as predominantly IGF-I or a closely related species and not IGF-II. Levels of approximately 15-50 ng IGF-I (based on human IGF-I standard)/10(6) islet cells accumulated in media after 72 h, and presumably represented synthesis by the islet cells. Concentrations of IGF-I attained in culture media, approximately 0.1 ng/ml, were sufficient to stimulate [3H]thymidine incorporation into B-cells. Growth hormone did not consistently increase IGF-I synthesis, suggesting that the previously described effects of growth hormone on islet cell replication do not result from stimulation of IGF-I synthesis by islet cells. Thus, although the IGF-I synthesized by islet cells may be a physiologically relevant growth factor for these cells, the mitogenic effects of growth hormone in islet cells appear to be independent and not mediated by IGF-I.
J A
JA
Romanus
A
A
Rabinovitch
M M
MM
Rechler
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002352:Carrier Proteins / Q000302:isolation & purification; D002478:Cells, Cultured; D002850:Chromatography, Gel; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D010452:Peptide Biosynthesis; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012756:Sheep; D013002:Somatomedins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology
D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D010455:Peptides; D013002:Somatomedins; D004247:DNA