PMID- 33187870 OWN - NLM STAT- MEDLINE DCOM- 20211223 LR - 20211223 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 35 IP - 1 DP - 2021 Jan TI - Metformin alters peripheral blood mononuclear cells (PBMC) senescence biomarkers gene expression in type 2 diabetic patients. PG - 107758 LID - S1056-8727(20)30539-0 [pii] LID - 10.1016/j.jdiacomp.2020.107758 [doi] AB - 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(INK4a), p53, and p21(Cip1/WAF), 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. LMNADelta10 and Progerin mRNA expression was not detected in PBMC of all groups. Expression of p16(INK4a), p21(Cip1/WAF) 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, TNFalpha, 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. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Al Dubayee, Mohammed AU - Al Dubayee M AD - 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. Electronic address: aldubayeemo@NGHA.med.sa. FAU - Alshahrani, Awad AU - Alshahrani A AD - 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. Electronic address: alshahraniaw@ksau-hs.edu.sa. FAU - Almalk, Malak AU - Almalk M AD - College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: almalki130@ksau-hs.edu.sa. FAU - Hakami, Alanoud AU - Hakami A AD - College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: hakami134@ksau-hs.edu.sa. FAU - Homoud, Bareen AU - Homoud B AD - College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: homoud205@ksau-hs.edu.sa. FAU - Alzneidi, Nowar AU - Alzneidi N AD - College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: alzneidi207@ksau-hs.edu.sa. FAU - Aldhalaan, Jumana AU - Aldhalaan J AD - College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: aldhalaan149@ksau-hs.edu.sa. FAU - Aljbli, Ghaidaa AU - Aljbli G AD - College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: aljbli162@ksau-hs.edu.sa. FAU - Nasr, Amre AU - Nasr A AD - College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: nasra@ksau-hs.edu.sa. FAU - Farahat, Ahmed I AU - Farahat AI AD - Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. FAU - Aljada, Ahmad AU - Aljada A AD - Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. Electronic address: aaljadaa@Alfaisal.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201007 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Biomarkers) RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) RN - 0 (RNA, Messenger) RN - 0 (Tumor Suppressor Protein p53) RN - 9100L32L2N (Metformin) SB - IM MH - Biomarkers MH - Cellular Senescence MH - Cyclin-Dependent Kinase Inhibitor p16/genetics MH - *Diabetes Mellitus, Type 2/complications/drug therapy/genetics MH - Gene Expression MH - Humans MH - Leukocytes, Mononuclear MH - Metformin/pharmacology/therapeutic use MH - Obesity MH - RNA, Messenger MH - Tumor Suppressor Protein p53/genetics MH - U937 Cells OTO - NOTNLM OT - Inflammation and cellular senescence OT - Insulin resistance OT - LMNA/C transcript variants OT - Mononuclear cells OT - Type 2 diabetes mellitus COIS- Declaration of competing interest All authors declare no conflicts of interest in relation to the work reported in this manuscript. All authors assure there's no financial/personal interest or belief that could affect their objectivity. EDAT- 2020/11/15 06:00 MHDA- 2021/12/24 06:00 CRDT- 2020/11/14 05:23 PHST- 2020/06/20 00:00 [received] PHST- 2020/09/11 00:00 [revised] PHST- 2020/09/26 00:00 [accepted] PHST- 2020/11/15 06:00 [pubmed] PHST- 2021/12/24 06:00 [medline] PHST- 2020/11/14 05:23 [entrez] AID - S1056-8727(20)30539-0 [pii] AID - 10.1016/j.jdiacomp.2020.107758 [doi] PST - ppublish SO - J Diabetes Complications. 2021 Jan;35(1):107758. doi: 10.1016/j.jdiacomp.2020.107758. Epub 2020 Oct 7.