Hyperproinsulinemia is associated with increased β cell demand after hemipancreatectomy in humans

Abstract

The cause of disproportionate hyperproinsulinemia in patients with type II diabetes is controversial. To examine whether increased β cell demand might contribute, we measured proinsulin and insulin concentrations in clinically healthy humans who had undergone hemipancreatectomy for the purpose of organ donation, a procedure previously demonstrated to increase β cell demand and diminish insulin secretory reserve capacity. Subjects were studied at least 1 yr after hemipancreatectomy. Seven donors were followed prospectively and served as their own controls. Nine additional donors were matched with normal controls (cross-sectional group). Fasting serum concentrations of intact proinsulin and conversion intermediates (total) were measured by a two-step radioimmunoassay; independent determinations of intact proinsulin and 32,33 split proinsulin were performed using an immunoradiometric assay. Serum total proinsulin values were significantly greater in hemipancreatectomized groups than controls (prospective group: predonation = 6.24±1.14 pM, postdonation = 34.63±17.47 pM, P < 0.005; cross-sectional group: controls = 5.78±1.12 pM, donors = 15.22±5.20 pM, P < 0.025). The ratio of total proinsulin to immunoreactive insulin was directly correlated with fasting plasma glucose and showed a significant inverse relationship to secretory reserve capacity. Both absolute and relative hyperproinsulinemia is found in hemipancreatectomized donors. These data demonstrate that partial pancreatectomy with its associated increase in β cell demand raises measures of proinsulin in humans.