BIMODAL EFFECT OF TRANSFORMING GROWTH-FACTOR-BETA ON INSULIN-SECRETION IN MIN6 CELLS

The effects of transforming growth factor-beta (TGF-beta) on insulin s ecretion were investigated using a glucose-responsive clonal cell line , MIN6. One hundred pM TGF-beta stimulated insulin release during 0.5- 24 h of incubation in the presence of 5.5 mM glucose, but not after 48 h; 1 nM TGF-beta also stimulated insulin release up to 2 h of exposur e, but the effect was not seen after 6 h of exposure. When cells were incubated with 25 mM glucose for 24 h, 100 pM TGF-beta significantly i nhibited glucose-stimulated insulin release, whereas insulin release w as not altered at 0 or 2.8 mM glucose. On the contrary, forskolin- (10 mu M) and tolbutamide- (40 mu M) induced insulin release were not aff ected by TGF-beta. TGF-beta affected neither the cell growth nor the c ellular insulin content. An addition of 1 mu M nitrendipine abolished TGF-beta-induced insulin secretion at 5.5 mM glucose. The present stud y shows that TGF-beta exerts a bimodal effect on glucose-induced insul in secretion from MIN6 cells, depending on dose, time of exposure and concentrations of coexisting glucose. These effects might be mediated by the Ca2+-dependent mechanism.