Stimulation by D-glucose of protein biosynthesis in tumoral insulin-producing cells (RINm5F line).

Abstract

Tumoral insulin-producing cells of the RINm5F line display a poor secretory response to D-glucose. Relative to basal insulin output, which corresponds to a fractional release of stored hormone close to 25%/90 min, the glucose-induced increment in insulin release does not exceed 28 +/- 7%. The low efficiency of D-glucose as an insulin secretagogue contrasts with a marked stimulant action of the hexose on peptide biosynthesis. Thus, D-glucose increases in a rapid, sustained, and dose-related manner the incorporation of [3H]leucine or [3H]phenylalanine into trichloroacetic acid-precipitable material; there is a 7-fold difference between basal and glucose-stimulated protein biosynthesis. Although the low proinsulin and insulin content of the tumoral cells, relative to their total protein content, hampers the quantification of newly synthesized hormonal products, the ratio of immunoreactive proinsulin to insulin exceeded the value in normal islet cells; this difference was more marked in secreted than stored material. It is concluded that despite their poor secretory response to D-glucose, the tumoral cells are, in fact, quite sensitive to this hexose, as documented by its effect on biosynthetic activity. Although RINm5F cells are known to display an acute secretory response to nonnutrient secretagogues, the apparent discrepancy between the biosynthetic and secretory responses to D-glucose may be accounted for in part by a severe perturbation in the capacity of the tumoral cells to store proinsulin and insulin.