Evidence of Extrapancreatic Glucagon Secretion in Man
Evidence of Extrapancreatic Glucagon Secretion in Man
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DOI：
10.2337/db15-1541
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发表时间：
2016-03-01
期刊：
影响因子：
7.7
通讯作者：
Knop, Filip K.
中科院分区：
文献类型：
--
作者：
Lund, Asger;Bagger, Jonatan I.;Knop, Filip K.
胰高血糖素被认为是一种胰腺特异性激素，高胰高血糖素血症已被证明对糖尿病患者的高血糖状态有显着影响。这种高胰高血糖素血症被认为是由于细胞对葡萄糖和胰岛素的抑制作用不敏感以及胰岛素分泌减少而引起的。我们假设吸收后高胰高血糖素血症代表一种肠道依赖性现象，并对 10 名完全胰腺切除的患者和 10 名健康对照受试者进行了 75 克口服葡萄糖耐量试验和相应的等血糖静脉葡萄糖输注。我们应用了血浆胰高血糖素的新颖分析方法（夹心 ELISA 和基于质谱的蛋白质组学），结果表明 29 个氨基酸胰高血糖素在没有胰腺的患者中循环，并且胃肠道的葡萄糖刺激在这些患者中引起显着的高胰高血糖素血症。这些发现强调了人类体内胰外胰高血糖素（可能源自肠道）的存在，并表明它可能在继发于全胰腺切除术的糖尿病中发挥作用。
Glucagon is believed to be a pancreas-specific hormone, and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from -cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy control subjects to a 75-g oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. We applied novel analytical methods of plasma glucagon (sandwich ELISA and mass spectrometry-based proteomics) and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gastrointestinal tract elicits significant hyperglucagonemia in these patients. These findings emphasize the existence of extrapancreatic glucagon (perhaps originating from the gut) in man and suggest that it may play a role in diabetes secondary to total pancreatectomy.