OPPOSITE EFFECTS OF BETA-CELL DIFFERENTIATION AND GROWTH ON PEG EXPRESSION IN HUMAN FETAL PANCREATIC-CELLS

Reg is a gene associated with regeneration of pancreatic islets. We ha ve 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 fe tal pancreatic cells. Culture for 7 days with 10 mM nicotinamide led t o 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 p-cells, did not significant ly affect reg expression in adult human islets (84 +/- 4% of control, n 2, NS). Thus, a higher level of endocrine differentiation is associa ted with a lower level of reg expression, and a higher rate of beta-ce ll replication results in increased reg transcription. These results p rovide the first evidence of a molecular marker, the reg gene, to dist inguish between proliferation and differentiation of human beta-cells.