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Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

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World Journal of Diabetes 2024年第4期15卷 606-622页

作者： Ashwin Kumar Shukla Komal Awasthi kauser usman Monisha Banerjee Molecular and Human Genetics Laboratory Department of ZoologyUniversity of LucknowLucknow 226007Uttar PradeshIndia Department of Medicine King Georges’Medical UniversityLucknow 226003Uttar PradeshIndia Institute of Advanced Molecular Genetics and Infectious Diseases(IAMGID)University of LucknowLucknow 226007Uttar PradeshIndia

Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 *** has affected over 768 million people worldwide,resulting in approx-imately 6900000 ***-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney *** indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic *** the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 *** converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a *** ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and *** ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 *** review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in *** treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.

关键词： Angiotensin-converting enzyme 2 Angiotensin-converting enzyme inhibitors Angiotensin-II receptor blockers Complex diseases COVID-19 Type 2 diabetes

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Pharmacogenetic studies update in type 2 diabetes mellitus

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World Journal of Diabetes 2016年第15期7卷 302-315页

作者： Shalini Singh kauser usman Monisha Banerjee Molecular and Human Genetics Laboratory Department of Zoology University of Lucknow Lucknow 226007 India Department of Medicine King George’s Medical University Lucknow 226003 India

Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs(OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters(SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.

关键词： Type 2 diabetes mellitus Pharmacogenetics Genetic variants Oral antidiabetic drugs Personalized medicine

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