Glucose transporter proteins in human insulinoma.
OBJECTIVE
To determine the reason patients with insulinoma are unable to cease insulin secretion during hypoglycemia.


METHODS
Five patients with insulinoma.


METHODS
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.
Temple University Hospital, Philadelphia, Pennsylvania.
G
G
Boden
E
E
Murer
M
M
Mozzoli
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D002096:C-Peptide / Q000097:blood; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D051275:Glucose Transporter Type 4; D006801:Humans; D007003:Hypoglycemia / Q000097:blood; D007328:Insulin / Q000097:blood*; D007340:Insulinoma / Q000097:blood / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D009363:Neoplasm Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000097:blood / Q000378:metabolism*
D001786:Blood Glucose; D002096:C-Peptide; D051275:Glucose Transporter Type 4; D007328:Insulin; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; C495692:SLC2A4 protein, human