Insulinoma with postprandial hypoglycemia and characteristic expression of GLUT2/GCK/GLP-1R

Hypoglycemia is the most popular symptom of insulinoma patients. There have been no reports investigating immunohistochemical differences in the expression levels of glucose transporters, glucokinase, and glucagon-like peptide-1 receptor in insulinoma cells according to the clinical phenotypes of hypoglycemia, in particular hypoglycemia in the postprandial state alone or in both fasting and postprandial states. We immunohistochemically analyzed the expression of glucose transporters 1-3, glucokinase, and glucagon-like peptide-1 receptor in insulinoma cells of the resected pancreas from six patients. The frequency of hypoglycemia of <70 mg/dL before breakfast at the fasting state in one patient with exclusively postprandial hypoglycemia and the other five patients with both fasting and postprandial hypoglycemia was 0% and 33-100%, respectively. We found that insulinoma cells in the patient with exclusively postprandial hypoglycemia showed the higher expression of glucose transporter 2, glucokinase, and glucagon-like peptide-1 receptor than those of almost all the other five patients exhibiting both fasting and postprandial hypoglycemia. Glucose transporter 1 and 3 expression was very limited or not detected in insulinoma cells from any of the patients. In addition, we revealed that there was reduced expression of glucokinase and glucagon-like peptide-1 receptor in the patients with quite frequent fasting hypoglycemia. These findings indicate that the increased glucose transporter 2 and reduced glucokinase and glucagon-like peptide-1 receptor expression levels in insulinoma cells might be associated with the clinical phenotypes of hypoglycemic profiles in insulinoma patients.