Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Int J Mol Sci. 2019 Oct 30;20(21):5416. doi: 10.3390/ijms20215416.
Glucagon circulates in concentrations in the low picomolar range, which is demanding regarding the sensitivity of the methods for quantification applied. In addition, the differential and tissue specific proteolytic processing of the glucagon precursor and the presence in of several glucagon-like sequences, not only in the precursor of glucagon, but also in a number of other peptides of the glucagon-secretin family of peptides, put special demands on the specificity of the assays. Finally, experience has shown that unspecific interference of plasma components has presented additional problems. All of these problems have resulted in a lot of diverging results concerning measured and reported glucagon responses in both humans and experimental animals that have and still are causing considerable debate and controversy. There is very solid evidence that glucagon is an important hormone in human and mammalian metabolism, but its precise physiological role in glucose and lipid metabolism and in metabolic disease has been difficult to establish, not least because of these difficulties. It was our purpose with this review to discuss the methods of glucagon quantification and discuss pitfalls and sources of error. We also reviewed some of the dogmas regarding glucagon secretion in the light of the methodological difficulties.
胰高血糖素在循环中以低皮摩尔浓度存在，这对应用的定量方法的灵敏度提出了很高的要求。此外，胰高血糖素前体的差异和组织特异性蛋白水解加工，以及不仅在胰高血糖素前体中，而且在许多其他胰高血糖素-促分泌素肽家族的肽中存在几种胰高血糖素样序列，对检测的特异性提出了特殊要求。最后，经验表明，血浆成分的非特异性干扰带来了额外的问题。所有这些问题导致了关于人类和实验动物测量和报告的胰高血糖素反应的大量分歧结果，这些结果仍在引起相当大的争论和争议。有非常确凿的证据表明，胰高血糖素是人类和哺乳动物代谢中的一种重要激素，但它在葡萄糖和脂质代谢以及代谢性疾病中的精确生理作用一直难以确定，部分原因正是由于这些困难。我们撰写这篇综述的目的是讨论胰高血糖素定量的方法，并讨论其中的陷阱和误差来源。我们还根据方法学的困难，回顾了一些关于胰高血糖素分泌的教条。
