PMID- 33758522 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220421 IS - 1178-7007 (Print) IS - 1178-7007 (Electronic) IS - 1178-7007 (Linking) VI - 14 DP - 2021 TI - Gene Expression Profiling of Apoptotic Proteins in Circulating Peripheral Blood Mononuclear Cells in Type II Diabetes Mellitus and Modulation by Metformin. PG - 1129-1139 LID - 10.2147/DMSO.S300048 [doi] AB - INTRODUCTION: Insulin resistance in obesity and type 2 diabetes mellitus (T2DM) is associated with cardiovascular complications such as atherosclerosis. On the other hand, the reduction of apoptosis in macrophages has been linked with accelerated atherosclerosis. Apoptosis is controlled by a different family of proteins including Bcl-2 and caspases. METHODS: To examine apoptosis in insulin resistance, we assessed the mRNA expression by qRT-PCR of several Bcl-2 family members, as well as caspase-3, -7, -8, and -9 in peripheral blood mononuclear cells (PBMCs) isolated from lean, obese, diabetic, and diabetic on metformin individuals. RESULTS: PBMCs of diabetic individuals exhibited reduced expression of caspase-7 and increased expression of Bcl-10, Bad, Bax, Bid, and caspase-3. T2DM on metformin group had significantly higher Bad, Bax, and caspase-7 expression. DISCUSSION: The moderate up-regulation of pro-apoptotic Bcl-10, Bax, Bad, Bid, and the effector caspase-3 coupled with inhibition of caspase-7 in circulating PBMCs of T2DM could be the result of increased inflammation in T2DM. Metformin treatment significantly inhibited the expression of Bcl-10, Bid, and caspase-3 and upregulated Bad/Bax/caspase-7 pathway suggesting the activation of Bad/Bax/caspase-7 apoptotic pathway. Further studies are warranted to elicit the underlying apoptotic pathways of PBMCs in T2DM and following metformin treatment. CI - (c) 2021 Al Dubayee et al. FAU - Al Dubayee, Mohammed AU - Al Dubayee M AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia. AD - Department of Medicine, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia. FAU - Alshahrani, Awad AU - Alshahrani A AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia. AD - Department of Medicine, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia. FAU - Aljada, Dana AU - Aljada D AD - College of Liberal Arts and Sciences, Hofstra University, Hempstead, NY, USA. FAU - Zahra, Mahmoud AU - Zahra M AD - Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. FAU - Alotaibi, Ahmed AU - Alotaibi A AUID- ORCID: 0000-0002-0366-3817 AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia. FAU - Ababtain, Ibrahim AU - Ababtain I AUID- ORCID: 0000-0001-5233-9450 AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia. FAU - Alnaim, Malik AU - Alnaim M AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia. FAU - Alahmari, Ali AU - Alahmari A AUID- ORCID: 0000-0002-6138-8964 AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia. FAU - Aljarallah, Abdullah AU - Aljarallah A AUID- ORCID: 0000-0003-2985-5515 AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia. FAU - Elahi, Muhammad Affan AU - Elahi MA AD - Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. FAU - Fakhoury, Hana M A AU - Fakhoury HMA AUID- ORCID: 0000-0001-9974-2108 AD - Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. LA - eng PT - Journal Article DEP - 20210315 PL - New Zealand TA - Diabetes Metab Syndr Obes JT - Diabetes, metabolic syndrome and obesity : targets and therapy JID - 101515585 PMC - PMC7979348 OTO - NOTNLM OT - BCl-10 OT - BCl-2 OT - PBMC OT - T2DM OT - apoptosis OT - caspase OT - peripheral blood mononuclear cells COIS- The authors report no conflicts of interest for this work and declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. EDAT- 2021/03/25 06:00 MHDA- 2021/03/25 06:01 PMCR- 2021/03/15 CRDT- 2021/03/24 06:44 PHST- 2021/01/17 00:00 [received] PHST- 2021/02/23 00:00 [accepted] PHST- 2021/03/24 06:44 [entrez] PHST- 2021/03/25 06:00 [pubmed] PHST- 2021/03/25 06:01 [medline] PHST- 2021/03/15 00:00 [pmc-release] AID - 300048 [pii] AID - 10.2147/DMSO.S300048 [doi] PST - epublish SO - Diabetes Metab Syndr Obes. 2021 Mar 15;14:1129-1139. doi: 10.2147/DMSO.S300048. eCollection 2021.