Growth hormone is a growth factor for the differentiated pancreatic beta-cell.
The regulation of the growth of the pancreatic beta-cell is poorly understood. There are previous indications of a role of GH in the growth and insulin production of the pancreatic islets. In the present study we present evidence for a direct long-term effect of GH on proliferation and insulin biosynthesis of pancreatic beta-cells in monolayer culture. In culture medium RPMI 1640 supplemented with 2% normal human serum islets or dissociated islet cells from newborn rats maintained their insulin-producing capacity. When supplemented with 1-1000 ng/ml pituitary or recombinant human GH the islet cells attached, spread out, and proliferated into monolayers mainly consisting of insulin-containing cells. The number of beta-cells in S-phase was increased from 0.9-6.5% as determined by immunochemical staining of bromodeoxyuridine incorporated into insulin-positive cells. The increase in cell number was accompanied with a continuous increase in insulin release to the culture medium reaching a 10- 20-fold increase after 2-3 months with a half-maximal effect at about 10 ng/ml human GH. The biosynthesis of (pro)insulin was markedly increased with a normal rate of conversion of proinsulin to insulin. It is concluded that GH is a potent growth factor for the differentiated pancreatic beta-cell.
Nielsen
J H
JH
Hagedorn Research Laboratory, Gentofte, Denmark.
Linde
S
S
Welinder
B S
BS
Billestrup
N
N
Madsen
O D
OD
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D013006:Growth Hormone / Q000494:pharmacology*; D007150:Immunohistochemistry; D007328:Insulin / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D011384:Proinsulin / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins
D007328:Insulin; D011994:Recombinant Proteins; D013006:Growth Hormone; D011384:Proinsulin; D001973:Bromodeoxyuridine