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高密度脂蛋白(HDL)及其亚组分对胰腺衍生β细胞胰岛素分泌和胆固醇外排的影响。

The influence of high-density lipoprotein (HDL) and HDL subfractions on insulin secretion and cholesterol efflux in pancreatic derived β-cells.

机构信息

Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga #15, Tlalpan, Belisario Domínguez Sección XVI, P.C. 14080, Mexico City, Mexico.

Research Unit on Metabolic Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

出版信息

J Endocrinol Invest. 2021 Sep;44(9):1897-1904. doi: 10.1007/s40618-021-01504-9. Epub 2021 Jan 24.

Abstract

BACKGROUND

High-density lipoprotein (HDL) is considered a complex plasma-circulating particle with subfractions that vary in function, size, and chemical composition. We sought to test the effects of HDL, and HDL subfractions on insulin secretion and cholesterol efflux in the β-cell line MIN-6.

METHODS

We used total HDL and HDL subfractions 2a, 2b, 3a, 3b, and 3c, isolated from human plasma, to test insulin secretion under different glucose concentrations as well as insulin content and cholesterol efflux in the insulinoma MIN-6 cell line.

RESULTS

Incubation of MIN-6 cells with low glucose and total HDL increased insulin release two-fold. Meanwhile, when high glucose and HDL were used, insulin release increased more than five times. HDL subfractions 2a, 2b, 3a, 3b, and 3c elicited higher insulin secretion and cholesterol efflux than their respective controls, at both low and high glucose concentrations. The insulin content of the MIN-6 cells incubated with low glucose and any of the five HDL subclasses had a modest reduction compared with their controls. However, there were no statistically significant differences between each HDL subfraction on their capacity of eliciting insulin secretion, insulin content, or cholesterol efflux.

CONCLUSIONS

HDL can trigger insulin secretion under low, normal, and high glucose conditions. We found that all HDL subfractions exhibit very similar capacity to increase insulin secretion and cholesterol efflux. This is the first report demonstrating that HDL subfractions act both as insulin secretagogues (under low glucose) and insulin secretion enhancers (under high glucose) in the MIN-6 cell line.

摘要

背景

高密度脂蛋白(HDL)被认为是一种复杂的血浆循环颗粒,其亚组分在功能、大小和化学成分上有所不同。我们试图测试 HDL 及其亚组分对 MIN-6 胰岛β细胞胰岛素分泌和胆固醇流出的影响。

方法

我们使用从人血浆中分离的总 HDL 和 HDL 亚组分 2a、2b、3a、3b 和 3c,在不同葡萄糖浓度下测试胰岛素分泌以及胰岛素瘤 MIN-6 细胞系中的胰岛素含量和胆固醇流出。

结果

在低葡萄糖和总 HDL 孵育 MIN-6 细胞可使胰岛素释放增加两倍。同时,当使用高葡萄糖和 HDL 时,胰岛素释放增加了五倍以上。HDL 亚组分 2a、2b、3a、3b 和 3c 在低葡萄糖和高葡萄糖浓度下均比各自的对照物引起更高的胰岛素分泌和胆固醇流出。与对照相比,在低葡萄糖和五种 HDL 亚类中孵育的 MIN-6 细胞的胰岛素含量略有降低。然而,在诱导胰岛素分泌、胰岛素含量或胆固醇流出方面,各 HDL 亚组分之间没有统计学上的显著差异。

结论

HDL 可在低、正常和高葡萄糖条件下触发胰岛素分泌。我们发现所有 HDL 亚组分都表现出非常相似的增加胰岛素分泌和胆固醇流出的能力。这是首次报道表明 HDL 亚组分在 MIN-6 细胞系中既作为胰岛素分泌激动剂(在低葡萄糖下)又作为胰岛素分泌增强剂(在高葡萄糖下)发挥作用。

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