二甲双胍改变 2 型糖尿病患者外周血单个核细胞（PBMC）衰老生物标志物基因表达。

Metformin alters peripheral blood mononuclear cells (PBMC) senescence biomarkers gene expression in type 2 diabetic patients.

机构信息

College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia; King Abdullah International Medical Research Center (KAIMRC), Saudi Arabia; Department of Medicine, Ministry of National Guard Health Affairs (MNG-HA), Saudi Arabia.

College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia.

出版信息

J Diabetes Complications. 2021 Jan;35(1):107758. doi: 10.1016/j.jdiacomp.2020.107758. Epub 2020 Oct 7.

DOI:10.1016/j.jdiacomp.2020.107758

PMID:33187870

Abstract

BACKGROUND

Although there is increasing evidence showing that cell senescence is increased in circulating PBMC in type 2 diabetes mellitus (T2DM), the data are contradictory. This study examined several senescence biomarkers, including LMNA/C transcript variants, p16, p53, and p21, in PBMC of T2DM patients and the effect of Metformin on these senescence markers.

METHODS

Blood samples were obtained from 30 lean, 30 obese, 20 newly diagnosed type 2 diabetes mellitus (T2DM), and 30 T2DM on Metformin. PBMC were isolated and mRNA expression of the senescence biomarkers were quantified by RT-qPCR. The effect of ectopic expression of LMNA and LMNC in human monocytic cells lines (THP-1 and U937) on several inflammatory mediators were also examined.

RESULTS

LMNA expression was significantly higher in PBMC of obese and T2DM patients. LMNC expression was significantly inhibited in T2DM patients. LMNAΔ10 and Progerin mRNA expression was not detected in PBMC of all groups. Expression of p16, p21 and p53 were inhibited significantly in T2DM. Metformin treatment reverted LMNA, LMNC, and p53 expression levels to normal levels. Upregulation of LMNA in monocytic THP-1 and U937 cell lines induced CD68, TNFα, CCL2, IL-6 and NOS2.

CONCLUSIONS

These data support the notion that LMNA may mediate senescence in PBMCs of T2DM by upregulating inflammatory pathways. Metformin may exert its anti-inflammatory property by modulation of senescence mediator LMNA.

摘要

背景

尽管越来越多的证据表明，2 型糖尿病（T2DM）患者循环 PBMC 中的细胞衰老增加，但数据存在矛盾。本研究检测了 T2DM 患者 PBMC 中的几种衰老生物标志物，包括 LMNA/C 转录变体、p16、p53 和 p21，以及二甲双胍对这些衰老标志物的影响。

方法

从 30 名瘦型、30 名肥胖型、20 名新诊断的 2 型糖尿病（T2DM）患者和 30 名服用二甲双胍的 T2DM 患者中采集血样。分离 PBMC，通过 RT-qPCR 定量检测衰老生物标志物的 mRNA 表达。还检测了异位表达 LMNA 和 LMNC 在人单核细胞系（THP-1 和 U937）中对几种炎症介质的影响。

结果

肥胖和 T2DM 患者的 PBMC 中 LMNA 表达显著升高。T2DM 患者的 LMNC 表达受到显著抑制。所有组的 PBMC 中均未检测到 LMNAΔ10 和 Progerin mRNA 表达。T2DM 患者中 p16、p21 和 p53 的表达显著受到抑制。二甲双胍治疗使 LMNA、LMNC 和 p53 的表达水平恢复正常。单核细胞 THP-1 和 U937 细胞系中 LMNA 的上调诱导了 CD68、TNFα、CCL2、IL-6 和 NOS2 的表达。