Therapy of Type 2 Diabetes in Patients with SARS-CoV-2 Infection

Bielka, Weronika; Przezak, Agnieszka; Pawlik, Andrzej

doi:10.3390/ijms22147605

Cited by 18 publications

(20 citation statements)

References 133 publications

(195 reference statements)

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“…Additionally, TKT activity is enhanced in diabetes patients [ 19 , 20 , 21 ] and diabetes patients are at a high risk from COVID-19 [ 4 , 5 , 6 ]. Given the potential role of TKT in SARS-CoV-2 replication identified here, elevated TKT levels may be one of the factors that predispose diabetes patients to experience severe COVID-19.…”

Section: Discussionmentioning

confidence: 99%

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Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

et al. 2021

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SARS-CoV-2 is causing the coronavirus disease 2019 (COVID-19) pandemic, for which effective pharmacological therapies are needed. SARS-CoV-2 induces a shift of the host cell metabolism towards glycolysis, and the glycolysis inhibitor 2-deoxy-d-glucose (2DG), which interferes with SARS-CoV-2 infection, is under development for the treatment of COVID-19 patients. The glycolytic pathway generates intermediates that supply the non-oxidative branch of the pentose phosphate pathway (PPP). In this study, the analysis of proteomics data indicated increased transketolase (TKT) levels in SARS-CoV-2-infected cells, suggesting that a role is played by the non-oxidative PPP. In agreement, the TKT inhibitor benfooxythiamine (BOT) inhibited SARS-CoV-2 replication and increased the anti-SARS-CoV-2 activity of 2DG. In conclusion, SARS-CoV-2 infection is associated with changes in the regulation of the PPP. The TKT inhibitor BOT inhibited SARS-CoV-2 replication and increased the activity of the glycolysis inhibitor 2DG. Notably, metabolic drugs like BOT and 2DG may also interfere with COVID-19-associated immunopathology by modifying the metabolism of immune cells in addition to inhibiting SARS-CoV-2 replication. Hence, they may improve COVID-19 therapy outcomes by exerting antiviral and immunomodulatory effects.

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Section: Discussionmentioning

confidence: 99%

“…Metabolic disorders and diabetes are associated with an increased risk of severe COVID-19 [ 4 , 5 , 6 ]. Increased amounts of glucose in the sera of COVID-19 patients were correlated with poor prognosis in individuals both with and without pre-existing diabetes [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

et al. 2021

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“…In addition, Esam Z. et al Also showed that the use of metformin could reduce the risk of lung fibrosis associated with SARS-Cov-2 (Esam 2020 ). There are numerous other studies in this area, all of which suggest that metformin may be a useful adjunctive therapy for COVID-19 patients (Bhutta et al 2021 , Bielka et al 2021 , Ibrahim et al 2021 , Varghese, Samuel et al 2021, Zangiabadian et al 2021 ).…”

Section: Metformin and Therapeutic Goalsmentioning

confidence: 99%

The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases

Hasanvand

2022

Inflammopharmacol

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Metformin can suppress gluconeogenesis and reduce blood sugar by activating adenosine monophosphate-activated protein kinase (AMPK) and inducing small heterodimer partner (SHP) expression in the liver cells. The main mechanism of metformin’s action is related to its activation of the AMPK enzyme and regulation of the energy balance. AMPK is a heterothermic serine/threonine kinase made of a catalytic alpha subunit and two subunits of beta and a gamma regulator. This enzyme can measure the intracellular ratio of AMP/ATP. If this ratio is high, the amino acid threonine 172 available in its alpha chain would be activated by the phosphorylated liver kinase B1 (LKB1), leading to AMPK activation. Several studies have indicated that apart from its significant role in the reduction of blood glucose level, metformin activates the AMPK enzyme that in turn has various efficient impacts on the regulation of various processes, including controlling inflammatory conditions, altering the differentiation pathway of immune and non-immune cell pathways, and the amelioration of various cancers, liver diseases, inflammatory bowel disease (IBD), kidney diseases, neurological disorders, etc. Metformin’s activation of AMPK enables it to control inflammatory conditions, improve oxidative status, regulate the differentiation pathways of various cells, change the pathological process in various diseases, and finally have positive therapeutic effects on them. Due to the activation of AMPK and its role in regulating several subcellular signalling pathways, metformin can be effective in altering the cells’ proliferation and differentiation pathways and eventually in the prevention and treatment of certain diseases. Graphical abstract

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“…However, T2DM therapy should be designed in accordance with local guidelines while taking personal parameters and comorbidities into account; therefore, current therapeutic regimens for the management of T2DM are not discussed here. Recent review articles about the management of COVID-19 in patients with T2DM have been published elsewhere [ 158 , 159 , 160 ].…”

Section: Prognosis Of T2dm Patients With Covid-19mentioning

confidence: 99%

Recent Progress in the Diagnosis and Management of Type 2 Diabetes Mellitus in the Era of COVID-19 and Single Cell Multi-Omics Technologies

Kupai

Várkonyi

Török

et al. 2022

Life

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Type 2 diabetes mellitus (T2DM) is one of the world’s leading causes of death and life-threatening conditions. Therefore, we review the complex vicious circle of causes responsible for T2DM and risk factors such as the western diet, obesity, genetic predisposition, environmental factors, and SARS-CoV-2 infection. The prevalence and economic burden of T2DM on societal and healthcare systems are dissected. Recent progress on the diagnosis and clinical management of T2DM, including both non-pharmacological and latest pharmacological treatment regimens, are summarized. The treatment of T2DM is becoming more complex as new medications are approved. This review is focused on the non-insulin treatments of T2DM to reach optimal therapy beyond glycemic management. We review experimental and clinical findings of SARS-CoV-2 risks that are attributable to T2DM patients. Finally, we shed light on the recent single-cell-based technologies and multi-omics approaches that have reached breakthroughs in the understanding of the pathomechanism of T2DM.

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Therapy of Type 2 Diabetes in Patients with SARS-CoV-2 Infection

Cited by 18 publications

References 133 publications

Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases

Recent Progress in the Diagnosis and Management of Type 2 Diabetes Mellitus in the Era of COVID-19 and Single Cell Multi-Omics Technologies

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