GLUCOSE-TRANSPORTER PROTEINS IN HUMAN INSULINOMA

Objective: To determine the reason patients with insulinoma are unable to cease insulin secretion during hypoglycemia. Patients: Five patien ts with insulinoma. Design: All patients fasted for up to 25 hours, du ring which blood was obtained serially for determination of glucose an d insulin concentrations. Insulinomas were surgically removed from all patients and Glut 1 and Glut 2 transporter proteins were measured in solubilized tumor membranes by immune blotting. Results: in all patien ts, serum insulin concentrations failed to decrease to less than 30.0 pmol/L (<5.0 mu U/mL) and C-peptide concentrations to less than 0.08 n mol/L during hypoglycemia (glucose concentration, <2.2 mmol/L) that wa s induced by fasting. The islet cell tumors from all five patients con tained Glut 1, a low-K-m glucose transporter protein, which is not nor mally present in beta-cells. Glut 2, a high-K-m glucose transporter pr otein, which is normally prevalent in beta-cells, was undetectable in one patient and was present in what appeared to be low concentrations in the remaining four patients. Conclusions: Our data are compatible w ith the concept that continued glucose transport, mediated by the low- K-m Glut 1 glucose transporter, was responsible for continued insulin release during hypoglycemia in these patients.