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Gene Expression Profiling of Apoptotic Proteins in Circulating Peripheral Blood Mononuclear Cells in Type II Diabetes Mellitus and Modulation by Metformin

Authors Al Dubayee M, Alshahrani A, Aljada D, Zahra M, Alotaibi A, Ababtain I, Alnaim M, Alahmari A, Aljarallah A, Elahi MA, Fakhoury HMA

Received 17 January 2021

Accepted for publication 23 February 2021

Published 15 March 2021 Volume 2021:14 Pages 1129—1139

DOI https://doi.org/10.2147/DMSO.S300048

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Juei-Tang Cheng


Mohammed Al Dubayee,1– 3 Awad Alshahrani,1– 3 Dana Aljada,4 Mahmoud Zahra,5 Ahmed Alotaibi,1 Ibrahim Ababtain,1 Malik Alnaim,1 Ali Alahmari,1 Abdullah Aljarallah,1 Muhammad Affan Elahi,5 Hana MA Fakhoury5

1College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia; 2King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia; 3Department of Medicine, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia; 4College of Liberal Arts and Sciences, Hofstra University, Hempstead, NY, USA; 5Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

Correspondence: Mohammed Al Dubayee
College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), P.O. Box 22490, Riyadh, Saudi Arabia
Tel +966 11 801 1111 ext: 53551
Email [email protected]

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.

Keywords: apoptosis, T2DM, peripheral blood mononuclear cells, PBMC, caspase, BCl-10, BCl-2

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