Plasma Proinsulin in Patients with Functioning Pancreatic Islet Cell Tumors1

Abstract

Plasma levels of proinsulin were determined in 19 patients with benign and in 2 patients with malignant insulin-producing islet cell tumors. Proinsulin accounted for 8–78 (mean 37)% of fasting plasma total immunoreactive insulin (IRI) in patients with islet cell tumors and for 20% or less in 10 healthy subjects. In 12 of 19 patients with benign and in both patients with malignant tumors, the proinsulin component was clearly elevated and exceeded 25% of fasting total IRI. The finding of an elevated fasting plasma level of proinsulin may be helpful in establishing the diagnosis of an insulin-producing islet cell tumor when fasting blood glucose is within the range of normal and/or when the plasma level of total IRI is normal or only slightly elevated. Fasting plasma concentrations of proinsulin were greater in those patients who had greater concentrations of total IRI, most likely reflecting the increased rate of insulin synthesis. In patients with benign tumors, the increases in plasma total IRI evoked by tolbutamide, leucine or arginine were due mainly to increases in the insulin component rather than to increases in proinsulin. This suggests that benign islet cell tumors retain the ability to convert proinsulin to insulin and to store and secrete insulin. Decreases in plasma total IRI induced by diazoxide were due to decreases both in insulin and proinsulin components. The decreases in plasma proinsulin were greater when diazoxide had been given orally for 2 days than when it was administered intravenously over 60 min. In 2 patients with benign tumors plasma IRI of portal venous blood contained a lesser proportion of proinsulin than did arterial blood. These latter observations suggest that proinsulin is removed more slowly from plasma than is the insulin component. The effect of streptozotocin upon plasma levels of insulin and proinsulin components was variable.