非糖尿病人群中ALDH1A3^(+)INS^(+)细胞与2型糖尿病风险因素的相关性研究  

ALDH1A3^(+)INS^(+)cells in non-diabetic subjects and risk for type 2 diabetes:Analysis of cross-sectional data

作　　者：刘腾丽 梁瑞 孙鹏 王乐[2] 刘娜 邹家琦 刘尧娟[2] 丁雪洁 王树森[2] Liu Tengli;Liang Rui;Sun Peng;Wang Le;Liu Na;Zou Jiaqi;Liu Yaojuan;Ding Xuejie;Wang Shusen(Organ Transplant Center,Tianjin First Central Hospital,Tianjin 300192,China;NHC Key Laboratory for Critical Care Medicine,Tianjin First Central Hospital,Tianjin 300384,China)

机构地区：[1]天津市第一中心医院器官移植中心,300192 [2]天津市第一中心医院卫生部危重病急救医学重点实验室,300384

出　　处：《中华内分泌代谢杂志》2022年第3期219-224,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(81870535,82070805,82100840,82100841);天津市自然科学基金(20JCQNJC01720);天津市"项目+团队"重点培养专项(XB202011)。

摘　　要：目的探究影响非糖尿病个体β细胞去分化水平的潜在2型糖尿病风险因素。方法通过胰岛素和β细胞去分化标志分子ALDH1A3免疫荧光染色法,检测38名非糖尿病和23例2型糖尿病患者胰腺切片中β细胞去分化水平。对非糖尿病个体胰岛β细胞去分化水平与年龄、体重指数、HbA1C、三酰甘油、总胆固醇等临床指标进行相关性分析。结果与非糖尿病个体相比,2型糖尿病患者胰岛内ALDH1A3^(+)INS^(+)细胞比例明显升高(P<0.001)。在糖尿病前期个体胰岛内ALDH1A3^(+)INS^(+)细胞比例降低(P=0.050),且与HbA1C值呈负相关(r=-0.44,P=0.006),但与年龄、体重指数无显著相关性。与血脂指标的相关性分析显示ALDH1A3^(+)INS^(+)细胞百分比与血浆总胆固醇水平呈正相关(r=0.39,P=0.045),但与三酰甘油无相关性。结论ALDH1A3^(+)INS^(+)细胞在糖尿病前期胰岛内显著降低,提示糖尿病前期可能存在β细胞身份的增强以代偿胰岛素分泌需求。ALDH1A3^(+)INS^(+)细胞在血浆总胆固醇水平较高的人群中升高,提示胆固醇可能是诱导β细胞去分化以及造成β细胞损伤的重要因素之一。Objective To investigate the correlations ofβcell dedifferentiation in non-diabetic subjects with risk factors for type 2 diabetes mellitus(T2DM).Methods Immunofluorescence staining with insulin andβcell dedifferentiated marker ALDH1A3 was used to evaluate theβcell dedifferentiation levels in 38 non-diabetic and 23 T2DM.Correlation analyses were performed betweenβcell dedifferentiation levels and available clinical parameters including age,body mass index,HbA1C level,triglycerides,and cholesterol levels in non-diabetic subjects.Resultsβcell dedifferentiation level defined by the positive expression of ALDH1A3 inβcells(ALDH1A3^(+)INS^(+)cell proportion)was significantly elevated in T2DM subjects(P<0.001).In PreD subjects,ALDH1A3^(+)INS^(+)cells proportion were decreased(P=0.050)and negatively correlated with HbA1C(r=-0.44,P=0.006),but not with age and body mass index.The analysis of correlation with lipidemic parameters showed that ALDH1A3^(+)INS^(+)cells proportion was positively correlated with plasma total cholesterol level(r=0.39,P=0.045),but not plasma total triglyceride.Conclusion ALDH1A3^(+)INS^(+)cells were found to be decreased in prediabetes,suggesting that there may be enhancedβ-cell identity in prediabetes to compensate for insulin secretion requirements;ALDH1A3^(+)INS^(+)cells were elevated in people with high plasma total cholesterol levels,suggesting that total cholesterol may be one of the factors that induceβ-cell dedifferentiation.

关 键 词：糖尿病 2型 β细胞去分化 总胆固醇 糖化血红蛋白 

分 类 号：R587.1[医药卫生—内分泌]