Opposite effects of beta-cell differentiation and growth on reg expression in human fetal pancreatic cells.
Reg is a gene associated with regeneration of pancreatic islets. We have previously shown that nicotinamide induces differentiation of human fetal beta-cells in tissue culture and that hepatocyte growth factor/scatter factor (HGF/SF) is mitogenic for the fetal beta-cells. We now tested whether these conditions, supporting either differentiation or growth, are associated with changes in reg gene expression in human fetal pancreatic cells. Culture for 7 days with 10 mM nicotinamide led to a fourfold decrease in reg mRNA levels (23 +/- 12% of control, n = 5, P < 0.001). In contrast, HGF/SF increased reg expression threefold (302 +/- 68% of control, n = 4, P < 0.05). Nicotinamide, which does not alter the differentiation level of adult beta-cells, did not significantly affect reg expression in adult human islets (84 +/- 4% of control, n = 2, NS). Thus, a higher level of endocrine differentiation is associated with a lower level of reg expression, and a higher rate of beta-cell replication results in increased reg transcription. These results provide the first evidence of a molecular marker, the reg gene, to distinguish between proliferation and differentiation of human beta-cells.
Otonkoski
T
T
Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
Mally
M I
MI
Hayek
A
A
D000591:Amino Acid Isomerases / Q000096:biosynthesis; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D002352:Carrier Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004706:Endodeoxyribonucleases / Q000096:biosynthesis; D005333:Fetus; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051847:Lithostathine; D009419:Nerve Tissue Proteins; D009536:Niacinamide / Q000494:pharmacology; D019696:Peptidylprolyl Isomerase; D010750:Phosphoproteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D051847:Lithostathine; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C497617:REG1A protein, human; D012333:RNA, Messenger; D009536:Niacinamide; D017228:Hepatocyte Growth Factor; D004706:Endodeoxyribonucleases; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase