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葡萄糖刺激的人胰岛分离物胰岛素分泌:它真的反映了β细胞在体内的功能吗?

Glucose-induced insulin secretion in isolated human islets: Does it truly reflect β-cell function in vivo?

机构信息

Unit of Endocrinology and Metabolism, Faculty of Medicine, University of Louvain, Brussels, Belgium.

出版信息

Mol Metab. 2021 Jun;48:101212. doi: 10.1016/j.molmet.2021.101212. Epub 2021 Mar 15.

DOI:10.1016/j.molmet.2021.101212
PMID:33737253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8065218/
Abstract

BACKGROUND

Diabetes always involves variable degrees of β-cell demise and malfunction leading to insufficient insulin secretion. Besides clinical investigations, many research projects used rodent islets to study various facets of β-cell pathophysiology. Their important contributions laid the foundations of steadily increasing numbers of experimental studies resorting to isolated human islets.

SCOPE OF REVIEW

This review, based on an analysis of data published over 60 years of clinical investigations and results of more recent studies in isolated islets, addresses a question of translational nature. Does the information obtained in vitro with human islets fit with our knowledge of insulin secretion in man? The aims are not to discuss specificities of pathways controlling secretion but to compare qualitative and quantitative features of glucose-induced insulin secretion in isolated human islets and in living human subjects.

MAJOR CONCLUSIONS

Much of the information gathered in vitro can reliably be translated to the in vivo situation. There is a fairly good, though not complete, qualitative and quantitative coherence between insulin secretion rates measured in vivo and in vitro during stimulation with physiological glucose concentrations, but the concordance fades out under extreme conditions. Perplexing discrepancies also exist between insulin secretion in subjects with Type 2 diabetes and their islets studied in vitro, in particular concerning the kinetics. Future projects should ascertain that the experimental conditions are close to physiological and do not alter the function of normal and diabetic islets.

摘要

背景

糖尿病总是涉及到不同程度的β细胞死亡和功能障碍,导致胰岛素分泌不足。除了临床研究,许多研究项目还使用啮齿动物胰岛来研究β细胞病理生理学的各个方面。它们的重要贡献为越来越多的依赖于分离的人胰岛的实验研究奠定了基础。

综述范围

本综述基于对 60 多年临床研究发表的数据和最近分离胰岛研究结果的分析,探讨了一个具有转化性质的问题。在体外用人胰岛获得的信息是否与我们对人类胰岛素分泌的认识相符?目的不是讨论控制分泌的途径的特异性,而是比较分离的人胰岛和活体人类受试者中葡萄糖诱导的胰岛素分泌的定性和定量特征。

主要结论

在体外收集的大量信息可以可靠地转化为体内情况。在刺激生理葡萄糖浓度时,在体内和体外测量的胰岛素分泌率之间存在相当好的、尽管不是完全的定性和定量一致性,但在极端条件下这种一致性消失了。在 2 型糖尿病患者及其体外研究的胰岛之间,胰岛素分泌也存在令人费解的差异,特别是在动力学方面。未来的项目应确定实验条件是否接近生理条件,并且不会改变正常和糖尿病胰岛的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfcc/8065218/4884356c235f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfcc/8065218/bb8b772153fd/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfcc/8065218/4884356c235f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfcc/8065218/bb8b772153fd/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfcc/8065218/4884356c235f/gr2.jpg

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