Biologically active circulating proinsulin-like materials from an islet cell carcinoma patient

Summary Circulating immunoreactive insulin (IRI) material was obtained from a hypoglycemic patient with a pancreatic islet cell carcinoma. On gel filtration, 85% of this material eluted as a homogeneous proinsulin peak (PLM) and 15% as insulin. On polyacrylamide gel electrophoresis, in addition to a small amount of insulin, two peaks were obtained. One had the migration of intact human proinsulin. The second electrophoresed as an intermediate species compatible with desdipeptide proinsulin. Trypsin treatment of PLM resulted in IRI material eluting as insulin on gel filtration. When comparable amounts of IRI material were tested, PLM showed about one half of the biological activity of porcine insulin in the rat hemidiaphragm system. No evidence of conversion to insulin was found after PLM had exerted its biological activity. In addition to large amounts of proinsulin, islet cell tumors may secrete significant amounts of intermediate species into the circulation.Supported by VA Research Funds and NIH Grant AM 11578