Glucose transporter proteins in human insulinoma

Abstract

Objective: To determine the reason patients with insulinoma are unable to cease insulin secretion during hypoglycemia.

Patients: Five patients with insulinoma.

Design: All patients fasted for up to 25 hours, during which blood was obtained serially for determination of glucose and 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 patients, serum insulin concentrations failed to decrease to less than 30.0 pmol/L (< 5.0 microU/mL) and C-peptide concentrations to less than 0.08 nmol/L during hypoglycemia (glucose concentration, < 2.2 mmol/L) that was induced by fasting. The islet cell tumors from all five patients contained Glut 1, a low-Km glucose transporter protein, which is not normally present in beta-cells. Glut 2, a high-Km glucose transporter protein, 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 with the concept that continued glucose transport, mediated by the low-Km Glut 1 glucose transporter, was responsible for continued insulin release during hypoglycemia in these patients.