The stimulatory effect of growth hormone, prolactin, and placental lactogen on beta-cell proliferation is not mediated by insulin-like growth factor-I.
The effects of GH, PRL, and placental lactogen (PL) on the proliferation of pancreatic beta-cells in vitro were studied as well as the possible effect of insulin-like growth factor-I (IGF-I) in mediating this effect. Proliferating beta-cells were identified by staining with a monoclonal antibody to bromodeoxyuridine (BrdU) after cells were incubated for 1 h in the presence of 10 microM BrdU. By double staining with insulin antibodies it was found that 6.3% of the beta-cells had incorporated BrdU when cultured for 7 days in the presence of 1 microgram/ml human GH (hGH) compared to 0.6% when cultured in the absence of hGH. Similar results were obtained using rat GH. The half-maximal effect of hGH on beta-cell proliferation was observed at 10 ng/ml, and the maximal effect at 100 ng/ml. Islet cells cultured in the presence of PRL or PL caused a dose-dependent increase in beta-cell proliferation similar to that caused by hGH. GH, PRL, and PL had no effect on the proliferation of glucagon- or somatostatin-producing cells. The addition of 100 ng/ml IGF-I to either control or GH-stimulated islet cells did not affect the labeling index. When GH-stimulated proliferation of beta-cells was measured in the presence of neutralizing concentrations of a rabbit IGF-I antiserum, the percentage of beta-cells incorporating BrdU was unaffected. Using Northern blot analysis, no IGF-I transcripts could be detected in RNA from GH-stimulated islets, whereas IGF-I transcripts were readily detected in RNA isolated from rat liver tissue. These data suggest that the stimulatory effect of GH, PRL, and PL on beta-cell proliferation is not mediated by IGF-I, but, rather, is a direct mitogenic effect on the beta-cell.
Hagedorn Research Laboratory, Gentofte, Denmark.
N
N
Billestrup
J H
JH
Nielsen
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005934:Glucagon / Q000096:biosynthesis; D013006:Growth Hormone / Q000494:pharmacology*; D007106:Immune Sera / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007515:Islets of Langerhans / Q000166:cytology*; D010928:Placental Lactogen / Q000494:pharmacology*; D011388:Prolactin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013004:Somatostatin / Q000096:biosynthesis
D007106:Immune Sera; D011994:Recombinant Proteins; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D013006:Growth Hormone; D005934:Glucagon; D010928:Placental Lactogen; D001973:Bromodeoxyuridine