In vitro biosynthesis and release of three immuno-reactive insulin-like components by a human insulinoma

Pieces of a human insulinoma were incubated for 120 or 180 min in media containing labelled leucine. In addition to insulin and proinsulin, the tumoral tissue was found to synthesize and release a third immunoreactive insulin-like component of higher molecular weight. No significant amount of the latter component was detected in normal rat islets under identical experimental conditions. The rate of secretion of insulin-like peptides was abnormally high relative to their concentration in the tumoral tissue, and was apparently unaffected by various insulinotropic or inhibitory agents. Only cycloheximide was found to significantly reduce the synthesis and subsequent release of insulin-like peptides by the tumoral tissue. It is suggested that the secretion of large amounts of both the high molecular weight component and proinsulin relative to that of insulin might be due, in part at least, to the inability of the tumoral cells to prevent the release of newly synthetized hormonal peptides, leading to the depletion of the tissue in hormonal products, as judged by both immunological and ultrastructural criteria.