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磺酰脲受体 1 和多药耐药蛋白 1 在调节人胰岛细胞瘤胰岛素分泌中的作用。

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

机构信息

Department of Endocrinology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2011 Feb;10(1):88-94. doi: 10.1016/s1499-3872(11)60013-1.

DOI:10.1016/s1499-3872(11)60013-1
PMID:21269941
Abstract

BACKGROUND

Sulfonylurea receptor 1 (SUR1) 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.

METHODS

Fasting 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, SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence.

RESULTS

Insulinoma 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 SUR1 increased, but MRP1 decreased in insulinoma compared with the adjacent islets.

CONCLUSIONS

The hypersecretion of insulin in insulinomas might be, at least partially, due to the enrichment of SUR1. In contrast, MRP1, which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.

摘要

背景

磺酰脲受体 1(SUR1)和多药耐药蛋白 1(MRP1)是与胰岛素分泌相关的多药耐药蛋白的两个主要成员。本研究旨在探讨其在胰岛素瘤中的表达及其在调节异常胰岛素分泌中的单独和协同作用。

方法

检测 11 例胰岛素瘤患者和 11 例健康对照者的空腹血糖、胰岛素和 C 肽。对 6 例胰岛素瘤患者进行了延长口服葡萄糖耐量试验。通过免疫组织化学检测 11 例胰岛素瘤患者的胰岛素含量、SUR1 和 MRP1。在 6 例胰岛素瘤患者中还通过免疫荧光法检测 SUR1 和 MRP1。

结果

胰岛素瘤患者表现出典型的 Whipple 三联征。每位胰岛素瘤患者的空腹血糖均低于 2.8mmol/L,同时胰岛素和 C 肽均增加。延长口服葡萄糖耐量试验显示,胰岛素瘤患者的胰岛素分泌也受到高血糖的刺激。免疫组织化学和免疫荧光染色显示,与相邻胰岛相比,胰岛素瘤中 SUR1 增加,而 MRP1 减少。

结论

胰岛素瘤中胰岛素的过度分泌可能至少部分归因于 SUR1 的富集。相反,在胰岛素瘤中下调的 MRP1 可能反映了胰岛素分泌的负反馈。

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