Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark; Department of Medicine, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Diabetes Res Clin Pract. 2019 Jan;147:19-28. doi: 10.1016/j.diabres.2018.06.013. Epub 2018 Jun 23.
Pancreatic alpha cells are generally considered the only source of glucagon secretion in humans. In the 1970s several groups investigating totally pancreatectomised animals reported that glucagon-like immunoreactive material could be detected in the gastrointestinal tract and reopened the question of an extrapancreatic source of glucagon proposed in 1948 when a hyperglycaemic substance was found in the gastrointestinal tract of dogs and rabbits. Nevertheless, over the years, controversy about the existence of extrapancreatic glucagon has flourished as it proved difficult to accurately measure fully processed 29-amino acid glucagon. Recent advances in analytical methods have increased sensitivity and specificity of glucagon assays and, furthermore, technical advances in mass spectrometry-based proteomics have made the detection of low-abundant peptides, such as glucagon, in human plasma more accurate. Here we review new data on extrapancreatic glucagon secretion in the context of historical data and recent analytical breakthroughs. Furthermore, the source, regulation and potential physiological role of extrapancreatic glucagon are discussed and ongoing challenges and knowledge-gaps are outlined.
胰腺α细胞通常被认为是人类胰高血糖素分泌的唯一来源。在 20 世纪 70 年代，一些研究完全胰切除动物的小组报告称，在胃肠道中可以检测到胰高血糖素样免疫反应物质，这重新引发了 1948 年提出的胰外胰高血糖素来源的问题，当时在狗和兔子的胃肠道中发现了一种高血糖物质。然而，多年来，关于胰外胰高血糖素存在的争议一直存在，因为很难准确测量完整加工的 29 个氨基酸的胰高血糖素。分析方法的最新进展提高了胰高血糖素检测的灵敏度和特异性，此外，基于质谱的蛋白质组学技术的进步使得在人血浆中检测低丰度肽（如胰高血糖素）更加准确。本文结合历史数据和最新的分析突破，综述了胰外胰高血糖素分泌的新数据。此外，还讨论了胰外胰高血糖素的来源、调节和潜在的生理作用，并概述了正在面临的挑战和知识空白。
