Associations of ATP-binding cassette transporter A1 and G1 with insulin secretion in human insulinomas.

OBJECTIVE

Adenosine triphosphate-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) are 2 important cholesterol transporters in human pancreatic β-cells. The aim of this study was to investigate their alteration in insulinomas and their potential associations with abnormal insulin secretion in these patients.

METHODS

Six patients with insulinoma and 6 healthy controls were recruited. Lipid profiles and glucose metabolism were measured. Insulin content, ABCA1, and ABCG1 in insulinomas and the adjacent islets of the 6 patients with insulinoma were detected by immunohistochemistry or immunofluorescence.

RESULTS

Plasma total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglyceride were comparable between the controls and the patients with insulinoma. Fasting glucose was less than 2.8 mmol/L, and insulin release index was greater than 0.3 in each patient. Serum insulin fell extremely, and blood glucose reached the reference range within an hour after the cutting of the tumors in 2 patients with insulinoma. Adenosine triphosphate-binding cassette transporter G1 increased in insulinomas compared with the adjacent islets. However, ABCA1 was detected neither in the adjacent islets nor in insulinomas. Adenosine triphosphate-binding cassette transporter G1 expression in insulinomas was significantly associated with fasting insulin level and insulin release index.

CONCLUSIONS

Increased ABCG1 may contribute to insulin hypersecretion in insulinomas. In contrast, the undetectable ABCA1 in insulinomas may reflect a negative feedback in insulin secretion in these patients.