中国兽医科学2025，Vol.55Issue(4)：552-562,11.DOI:10.16656/j.issn.1673-4696.2025.0105
长期高脂饮食导致人源化hIAPP+/-小鼠胰岛β细胞丢失的作用机制研究
Mechanism of long-term high-fat diet caused pancreatic β cell loss in humanized hIAPP+/-mice
摘要
Abstract
The coordination of multiple factors is critical to the pathological formation of T2DM.The purpose of this study was to explore the roles of age,diet and heredity in the pathogenesis of T2DM,as well as underlying mechanisms of endoplasmic reticulum(ER)-unfolded protein response(UPR)and mito-chondrial in pancreatic islet cells.hIAPP transgenic mice were fed with a high-fat diet for 6 and 12 months,the amylin deposition,apoptosis and proliferation of islets were measured by immunofluorescence and immunohistochemistry.Furthermore,islet cells were isolated,and the molecular changes related to ER-UPR and mitochondrial function regulation were detected by qPCR.The results showed that a high-fat diet decreased insulin sensitivity(P＜0.05)in hIAPP transgenic mice treated for 12 months,associated with islet cells loss,decreased islet cell proliferation(P＜0.05)and increased islet cell apoptosis(P＜0.001).Islet cells mitochondrial dysfunction and ER stress increased.The above results suggest that the severity of islet pathology in T2DM is closely related to the duration of high-fat diet.Long-term high-fat diet aggravated the molecular pathology of T2DM(amylin deposition in islet),impli-cated in aberration of ER and mitochondria,resulting in irreversible damage and dysfunction of the pan-creatic β cell.关键词
高脂饮食/内质网和线粒体/胰岛/hIAPPKey words
high-fat diet/ER and mitochondrial/islet/hIAPP分类
畜牧业引用本文复制引用
孙婧,郭家熙,陈海超,曹嘉芯,席晓霞..长期高脂饮食导致人源化hIAPP+/-小鼠胰岛β细胞丢失的作用机制研究[J].中国兽医科学,2025,55(4):552-562,11.基金项目
甘肃省自然科学基金实验动物专项(23JRRA1169):基于多重巢式PCR的实验动物病原菌检测方法建立及应用研究 （23JRRA1169）
