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Metformin alters peripheral blood mononuclear cells (PBMC) senescence biomarkers gene expression in type 2 diabetic patients.
Al Dubayee, Mohammed; Alshahrani, Awad; Almalk, Malak; Hakami, Alanoud; Homoud, Bareen; Alzneidi, Nowar; Aldhalaan, Jumana; Aljbli, Ghaidaa; Nasr, Amre; Farahat, Ahmed I; Aljada, Ahmad.
Afiliação
  • Al Dubayee M; 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
  • Alshahrani A; 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.ed
  • Almalk M; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: almalki130@ksau-hs.edu.sa.
  • Hakami A; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: hakami134@ksau-hs.edu.sa.
  • Homoud B; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: homoud205@ksau-hs.edu.sa.
  • Alzneidi N; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: alzneidi207@ksau-hs.edu.sa.
  • Aldhalaan J; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: aldhalaan149@ksau-hs.edu.sa.
  • Aljbli G; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: aljbli162@ksau-hs.edu.sa.
  • Nasr A; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Electronic address: nasra@ksau-hs.edu.sa.
  • Farahat AI; Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
  • Aljada A; Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. Electronic address: aaljadaa@Alfaisal.edu.
J Diabetes Complications ; 35(1): 107758, 2021 01.
Article em En | MEDLINE | ID: mdl-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, p16INK4a, p53, and p21Cip1/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. LMNAΔ10 and Progerin mRNA expression was not detected in PBMC of all groups. Expression of p16INK4a, p21Cip1/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, 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diabetes Mellitus Tipo 2 Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diabetes Mellitus Tipo 2 Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article