Gene Expression Profiling of Apoptotic Proteins in Circulating Peripheral Blood Mononuclear Cells in Type II Diabetes Mellitus and Modulation by Metformin
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 Science...
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Dove Medical Press
2021
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oai:doaj.org-article:efe7dd7df53d4d3789d196f380dda49a2021-12-02T18:23:04ZGene Expression Profiling of Apoptotic Proteins in Circulating Peripheral Blood Mononuclear Cells in Type II Diabetes Mellitus and Modulation by Metformin1178-7007https://doaj.org/article/efe7dd7df53d4d3789d196f380dda49a2021-03-01T00:00:00Zhttps://www.dovepress.com/gene-expression-profiling-of-apoptotic-proteins-in-circulating-periphe-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Mohammed 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 ArabiaCorrespondence: Mohammed Al DubayeeCollege of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), P.O. Box 22490, Riyadh, Saudi ArabiaTel +966 11 801 1111 ext: 53551Email ALDUBAYEEMO@ngha.med.saIntroduction: 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-2Al Dubayee MAlshahrani AAljada DZahra MAlotaibi AAbabtain IAlnaim MAlahmari AAljarallah AElahi MAFakhoury HMADove Medical Pressarticleapoptosist2dmperipheral blood mononuclear cells (pbmc)caspasebcl-10bcl-2Specialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 1129-1139 (2021) |
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apoptosis t2dm peripheral blood mononuclear cells (pbmc) caspase bcl-10 bcl-2 Specialties of internal medicine RC581-951 |
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apoptosis t2dm peripheral blood mononuclear cells (pbmc) caspase bcl-10 bcl-2 Specialties of internal medicine RC581-951 Al Dubayee M Alshahrani A Aljada D Zahra M Alotaibi A Ababtain I Alnaim M Alahmari A Aljarallah A Elahi MA Fakhoury HMA Gene Expression Profiling of Apoptotic Proteins in Circulating Peripheral Blood Mononuclear Cells in Type II Diabetes Mellitus and Modulation by Metformin |
| description |
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 ArabiaCorrespondence: Mohammed Al DubayeeCollege of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), P.O. Box 22490, Riyadh, Saudi ArabiaTel +966 11 801 1111 ext: 53551Email ALDUBAYEEMO@ngha.med.saIntroduction: 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 |
| format |
article |
| author |
Al Dubayee M Alshahrani A Aljada D Zahra M Alotaibi A Ababtain I Alnaim M Alahmari A Aljarallah A Elahi MA Fakhoury HMA |
| author_facet |
Al Dubayee M Alshahrani A Aljada D Zahra M Alotaibi A Ababtain I Alnaim M Alahmari A Aljarallah A Elahi MA Fakhoury HMA |
| author_sort |
Al Dubayee M |
| title |
Gene Expression Profiling of Apoptotic Proteins in Circulating Peripheral Blood Mononuclear Cells in Type II Diabetes Mellitus and Modulation by Metformin |
| title_short |
Gene Expression Profiling of Apoptotic Proteins in Circulating Peripheral Blood Mononuclear Cells in Type II Diabetes Mellitus and Modulation by Metformin |
| title_full |
Gene Expression Profiling of Apoptotic Proteins in Circulating Peripheral Blood Mononuclear Cells in Type II Diabetes Mellitus and Modulation by Metformin |
| title_fullStr |
Gene Expression Profiling of Apoptotic Proteins in Circulating Peripheral Blood Mononuclear Cells in Type II Diabetes Mellitus and Modulation by Metformin |
| title_full_unstemmed |
Gene Expression Profiling of Apoptotic Proteins in Circulating Peripheral Blood Mononuclear Cells in Type II Diabetes Mellitus and Modulation by Metformin |
| title_sort |
gene expression profiling of apoptotic proteins in circulating peripheral blood mononuclear cells in type ii diabetes mellitus and modulation by metformin |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/efe7dd7df53d4d3789d196f380dda49a |
| work_keys_str_mv |
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1718378133860646912 |