Carpéné Christian, Mauriège Pascale, Boulet Nathalie, Biron Simon, Grolleau Jean-Louis, Garcia-Barrado Maria José, Iglesias-Osma Mari Carmen
Institute of Metabolic and Cardiovascular Diseases, INSERM, UMR1048, Team 1, 31432 Toulouse, France.
I2MC, University of Toulouse, UMR1048, Paul Sabatier University, 31432 Toulouse, France.
Medicines (Basel). 2019 Aug 12;6(3):89. doi: 10.3390/medicines6030089.
: Methylamine, a natural soluble amine present in foods, is known to be a substrate of primary amine oxidase (PrAO) widely expressed in animal tissues. Methylamine has been reported to activate glucose transport in fat cells and to facilitate glucose disposal in rabbits but the interests and limits of such insulin-mimicking actions have not been further explored. This work aimed to perform a preclinical study of the inter-individual variations of these biological properties to study the putative link between PrAO activity and insulin resistance. : Methylamine was tested on human adipocyte preparations and in rabbit pancreatic islets to determine its influence on glucose uptake and insulin release, respectively. PrAO activity and related responses were determined in adipose tissues obtained from two cohorts of non-obese and obese women. : Adipose tissue PrAO activity was negatively correlated with insulin resistance in high-risk obese women. PrAO-dependent activation of glucose uptake was negatively correlated with body mass index and reflected the decrease of insulin responsiveness of human fat cells with increasing obesity. Methylamine exhibited antilipolytic properties in adipocytes but was unable to directly activate insulin secretion in isolated pancreatic islets. : PrAO activation by its substrates, e.g., methylamine, increases glucose utilization in human adipocytes in a manner that is linked to insulin responsiveness. Methylamine/PrAO interaction can therefore contribute to adipose tissue enlargement but should be considered as potentially useful for diabetes prevention since it could limit lipotoxicity and facilitate glucose handling, at the expense of favoring healthy fat accumulation.
甲胺是食物中天然存在的一种可溶性胺，已知它是在动物组织中广泛表达的伯胺氧化酶（PrAO）的底物。据报道，甲胺可激活脂肪细胞中的葡萄糖转运，并促进兔子体内的葡萄糖代谢，但这种胰岛素模拟作用的益处和局限性尚未得到进一步探索。这项工作旨在对这些生物学特性的个体间差异进行临床前研究，以探讨PrAO活性与胰岛素抵抗之间的潜在联系。在人体脂肪细胞制剂和兔胰岛中对甲胺进行了测试，以分别确定其对葡萄糖摄取和胰岛素释放的影响。在从两组非肥胖和肥胖女性获得的脂肪组织中测定了PrAO活性和相关反应。在高危肥胖女性中，脂肪组织PrAO活性与胰岛素抵抗呈负相关。PrAO依赖性葡萄糖摄取激活与体重指数呈负相关，反映了随着肥胖程度增加，人体脂肪细胞胰岛素反应性降低。甲胺在脂肪细胞中表现出抗脂解特性，但在分离的胰岛中不能直接激活胰岛素分泌。其底物（如甲胺）激活PrAO，以与胰岛素反应性相关的方式增加人体脂肪细胞中的葡萄糖利用。因此，甲胺/PrAO相互作用可能导致脂肪组织增大，但由于它可以限制脂毒性并促进葡萄糖处理，尽管以有利于健康脂肪积累为代价，仍应被视为对糖尿病预防可能有用。
