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.