EXPRESSION OF THE TRANSACTIVE FACTORS THAT STIMULATE INSULIN CONTROL ELEMENT-MEDIATED ACTIVITY APPEAR TO PRECEDE INSULIN GENE-TRANSCRIPTION

Cell type-specific expression of the major differentiated products of alpha (glucagon) and beta (insulin) cells are regulated by sequences f ound within their 5'-flanking region. Specific transcription of the in sulin gene appears to be principally controlled by a single cis-acting DNA element, termed the insulin control element (ICE). The ICE activa tor acts in combination with other positive regulatory factors that in teract within this region to generate the correct, cell type-specific expression. In the present study, we show that the ICE activator is no t only present but is functionally active in the islet glucagon-produc ing alpha cell line, alphaTC6. Analysis of the expression of various t ransfected insulin enhancer expression plasmids demonstrated that the insulin enhancer is active in alphaTC6 cells, although at a lower leve l than in beta cells. The reduced transcription from these constructs appears to be a consequence of the lack of other essential positive re gulator(s). The alphaTC6 cells were also shown to display neuronal-lik e properties. Since islet cells appear to evolve from an alpha-like pr ecursor cell that transiently expresses neuronal cell markers, these r esults would indicate that the ICE activator factor is induced before transcription of the insulin gene in the developing islet.