Mourad Nizar I, Xhema Daela, Gianello Pierre
Pôle de chirurgie expérimentale et transplantation, Université catholique de Louvain, Brussels, Belgium.
Front Endocrinol (Lausanne). 2022 Aug 11;13:935060. doi: 10.3389/fendo.2022.935060. eCollection 2022.
The potential use of porcine islets for transplantation in humans has triggered interest in understanding porcine islet physiology. However, the number of studies dedicated to this topic has remained limited, as most islet physiologists prefer to use the less time-consuming rodent model or the more clinically relevant human islet. An often-overlooked aspect of pig islet physiology is its alpha cell activity and regulation of its glucagon secretion. islet perifusion is a reliable method to study the dynamics of hormone secretion in response to different stimuli. We thus used this method to quantify and study glucagon secretion from pig islets. Pancreatic islets were isolated from 20 neonatal (14 to 21-day old) and 5 adult (>2 years) pigs and cultured in appropriate media. Islet perifusion experiments were performed 8 to 10 days post-isolation for neonatal islets and 1 to 2 days post-isolation for adult islets. Insulin and glucagon were quantified in perifusion effluent fractions as well as in islet extracts by RIA. Increasing glucose concentration from 1 mM to 15 mM markedly inhibited glucagon secretion independently of animal age. Interestingly, the effect of high glucose was more drastic on glucagon secretion compared to its effect on insulin secretion. , glucose injection during IVGTT initiated a quick (2-10 minutes) 3-fold decrease of plasmatic glucagon whereas the increase of plasmatic insulin took 20 minutes to become significant. These results suggest that regulation of glucagon secretion significantly contributes to glucose homeostasis in pigs and might compensate for the mild changes in insulin secretion in response to changes in glucose concentration.
猪胰岛在人类移植中的潜在应用引发了人们对了解猪胰岛生理学的兴趣。然而,致力于该主题的研究数量仍然有限,因为大多数胰岛生理学家更喜欢使用耗时较少的啮齿动物模型或临床相关性更高的人类胰岛。猪胰岛生理学中一个经常被忽视的方面是其α细胞活性及其胰高血糖素分泌的调节。胰岛灌流是研究激素分泌对不同刺激反应动态的可靠方法。因此,我们使用这种方法来量化和研究猪胰岛的胰高血糖素分泌。从20只新生(14至21日龄)和5只成年(>2岁)猪中分离出胰岛,并在适当的培养基中培养。新生胰岛在分离后8至10天进行胰岛灌流实验,成年胰岛在分离后1至2天进行。通过放射免疫分析(RIA)对灌流流出液部分以及胰岛提取物中的胰岛素和胰高血糖素进行定量。将葡萄糖浓度从1 mM增加到15 mM可显著抑制胰高血糖素分泌,且与动物年龄无关。有趣的是,高葡萄糖对胰高血糖素分泌的影响比对胰岛素分泌的影响更为显著。静脉葡萄糖耐量试验(IVGTT)期间注射葡萄糖可使血浆胰高血糖素迅速(2至10分钟)降低3倍,而血浆胰岛素的增加则需要20分钟才变得显著。这些结果表明,胰高血糖素分泌的调节对猪的葡萄糖稳态有显著贡献,并且可能补偿胰岛素分泌因葡萄糖浓度变化而产生的轻微变化。