Proinsulin and insulin release with a human insulinoma and adjacent nonadenomatous pancreas

The availability of surgically obtained samples of an insulin secreting human islet cell adenoma and adjacent nonadenomatous pancreas permitted studies in vitro of biosynthesis and release of proinsulin and insulin moieties. Acid-alcohol extracts of plasma, tumor and normal pancreas were subjected to gel nitration on Sephadex G-50 columns. IRI (immunoreactive insulin and proinsulin) were measured. Proinsulin in tumor represented 40% of the total IRI, in serum 37%, while in normal pancreas, it was only S%. Studies of unlabelled proinsulin and insulin release revealed that normal human pancreas responded in a manner similar to that reported for normal pancreas of the rat. In the absence of glucose, there was little insulin release. In the presence of glucose, insulin release increased and diazoxide and epinephrine inhibited this glucose effect. No proinsulin release could be found at any time. In contrast, the tumor released proinsulin rapidly even in the absence of glucose, while insulin release was nil. Glucose stimulated release of proinsulin and insulin, but preferentially insulin. Diazoxide had essentially no inhibitory effect on release of either moiety, while epinephrine inhibited release primarily of insulin and partially proinsulin. Biosynthetic studies with 3H-leucine were conducted only with the tumor tissue. Media and tissue were analyzed separately for labelled IRI moieties in the presence of glucose, diazoxide and epinephrine. Release of labelled proinsulin and insulin differed from data obtained with unlabelled materials and also from reported data using normal rat islets. It is concluded that in this insulinoma, stimulators and inhibitors of insulin release effect proinsulin to a lesser degree than insulin and that the responses of this tumor differ from those of normal human pancreas. Finally, it is postulated that newly synthesized moieties may not exist in a common pool with stored insulin moieties.