HIT cells secrete β-cell mitogenic factors

We studied the growth characteristics of the insulin-producing HIT cells. Although successful in many cell lines such as βTC1, growth arrest could not be obtained with HIT cells left for 3 days without serum. Cytofluorometric analysis showed that about 24% of the cells continuously exposed to serum peaked in the S phase. A similar proportion was found for cells cultured for 1 or 2 days in serum-free medium. A treatment with suramin, disrupting the binding of ligands from their receptors, was associated with a rapid and transient increase in c-fos and c-jun gene expression after suramin removal, in the absence of serum. In addition, HIT cells secrete mitogenic factors, different from IGF-I or IGF-II, acting on insulin-secreting βTC1 cells and on BP-A31 fibroblasts. Chromatography of the medium conditioned by the HIT cells on gel filtration gave two major mitogenic fractions, of hydrodynamic characteristics 33 000 and 3000-10 000. The activity was heat stable and bound to heparin. Comparative studies of the self-regulatory HIT cells, with the βTC1 cells requiring external growth factors, should contribute significantly to our understanding of the regulation of β cell growth.