Abstract
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
Highlights
Having the chemical formula of CH3 NH2, methylamine is the simplest methylated amine that belongs to the class of organic osmolytes, which are low-molecular weight compounds influencingMedicines 2019, 6, 89; doi:10.3390/medicines6030089 www.mdpi.com/journal/medicinesMedicines 2019, 6, 89 the properties of biological fluids and maintaining cell integrity
Studied in various mouse and rat models of diabetes and obesity, methylamine actions have been poorly investigated in humans
[50], it was we decided to work demonstrated with freshly isolated rabbit islets, in view of the improvement of conditions glucose utilization previously in vivo for rabbit islets, in view of the improvement of glucose utilization we previously demonstrated in vivo methylamine in this animal model [19]
Summary
Having the chemical formula of CH3 NH2 , methylamine is the simplest methylated amine that belongs to the class of organic osmolytes, which are low-molecular weight compounds influencingMedicines 2019, 6, 89; doi:10.3390/medicines6030089 www.mdpi.com/journal/medicinesMedicines 2019, 6, 89 the properties of biological fluids and maintaining cell integrity. Several microorganisms can grow when using methylamine as the sole source of carbon and nitrogen [5,6,7,8] while many other bacterial strains produce methylamine as one of the multiple volatile organic compounds they release in their environment In several cases, such production is endowed with antimicrobial activity [9], controlling thereby the biodiversity of the surrounding bacterial population (either in the gut or in foods during their processing). 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
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