Roles of sulfonylurea receptor 1 and multidrug resistance protein 1 in modulating insulin secretion in human insulinoma

BackgroundSulfonylurea receptor 1 (SURI) and multidrug resistance protein 1 (MRP1) are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion.MethodsFasting glucose, insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma patients. Insulin content, SURI and MRP1 were detectedin 11 insulinoma patients by immunohistochemistry SURI and MRP1 were also detected in 6 insulinoma patients by immunofluorescence.ResultsInsulinoma patients presented the typical demonstrations of Whipple's triad. Fasting glucose of each insulinoma patient was lower than 2.8 mmol/L, and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high glucose. Immunohistochemistry and immunofluorescence staining showed that SURI increased, but MRP1 decreased in insulinoma compared with the adjacent islets.ConclusionsThe hypersecretion of insulin in insulinomas might be, at least partially, due to the enrichment of SURI. In contrast, MRP1, which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.