Serine administration as a novel prophylactic approach to reduce the severity of acute pancreatitis during diabetes in mice.

摘要: Aims/hypothesis: Compared with the general population, individuals diabetes have a higher risk of developing severe acute pancreatitis, highly debilitating and potentially lethal inflammation exocrine pancreas. In this study, we investigated whether 1-deoxysphingolipids, atypical lipids that increase in circulation following development diabetes, exacerbate severity pancreatitis diabetic setting. Methods: We analysed administration an l-serine-enriched diet to mouse models established method for decreasing synthesis 1-deoxysphingolipids vivo, reduced pancreatitis. Furthermore, elucidated molecular mechanisms underlying lipotoxicity exerted by towards rodent pancreatic acinar cells vitro. Results: demonstrated l-serine supplementation damage tissue resulting from induction mice (average histological score: 1.5 l-serine-treated vs 2.7 control group). At cellular level, showed decreased production reactive oxygen species, endoplasmic reticulum stress apoptosis tissue. Importantly, these parameters, together DNA damage, were triggered upon treatment vitro, suggesting are cytotoxic cell-autonomous manner. search initiating events observed cytotoxicity, discovered induced early mitochondrial dysfunction cells, characterised ultrastructural alterations, impaired consumption rate ATP synthesis. Conclusions/interpretation: Our results suggest directly functionality highlight may be used as promising prophylactic intervention reduce context diabetes.