The complex combination of COVID-19 and diabetes: pleiotropic changes in glucose metabolism

Mahrooz, Abdolkarim; Muscogiuri, Giovanna; Buzzetti, Raffaella; Maddaloni, Ernesto

doi:10.1007/s12020-021-02729-7

Cited by 35 publications

(29 citation statements)

References 81 publications

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“…Notably, a metabolic shift towards glycolysis and PPP may also be involved in the inflammatory processes that are associated with COVID-19 progression to severe, life-threatening disease stages [ 9 , 43 , 44 , 45 ]. Moreover, reports show that a number of COVID-19 survivors suffer from metabolic disorders including abnormal glucose metabolism resulting in the metabolic derailment of immune cells [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

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%

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

et al. 2021

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“…Moreover, the virus sequesters the host's mitochondrial function and shifts it from aerobic to anaerobic [5]. In this state, the pyruvate produced from glucose during glycolysis is oxidized to lactate, thereby increasing glucose levels in the cytosol and leading to the generation of limited amounts of adenosine-5-triphosphate (ATP) [5,6]. The viral replication also consumes large amounts of ATP and therefore, its concentration is depleted.…”

Section: Introductionmentioning

confidence: 99%

Hyperglycemia and Loss of Redox Homeostasis in COVID-19 Patients

Soto

Guarner-Lans

Díaz-Díaz

et al. 2022

Cells

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The infection with SARS-CoV-2 impairs the glucose–insulin axis and this contributes to oxidative (OS) and nitrosative (NSS) stress. Here, we evaluated changes in glucose metabolism that could promote the loss of redox homeostasis in COVID-19 patients. This was comparative cohort and analytical study that compared COVID-19 patients and healthy subjects. The study population consisted of 61 COVID-19 patients with and without comorbidities and 25 healthy subjects (HS). In all subjects the plasma glucose, insulin, 8-isoprostane, Vitamin D, H2S and 3-nitrotyrosine were determined by ELISA. The nitrites (NO2−), lipid-peroxidation (LPO), total-antioxidant-capacity (TAC), thiols, glutathione (GSH) and selenium (Se) were determined by spectrophotometry. The glucose, insulin and HOMA-IR (p < 0.001), 8-isoprostanes, 3-nitrotyrosine (p < 0.001) and LPO were increased (p = 0.02) while Vitamin D (p = 0.01), H2S, thiols, TAC, GSH and Se (p < 0.001) decreased in COVID-19 patients in comparison to HS. The SARS-CoV-2 infection resulted in alterations in the glucose–insulin axis that led to hyperglycemia, hyperinsulinemia and IR in patients with and without comorbidities. These alterations increase OS and NSS reflected in increases or decreases in some oxidative markers in plasma with major impact or fatal consequences in patients that course with metabolic syndrome. Moreover, subjects without comorbidities could have long-term alterations in the redox homeostasis after infection.

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“…With the SARS-CoV-2 pandemic, data suggest that patients with underlying conditions, including diabetes, have more severe infections and sequelae. SARS-CoV-2, as an RNA virus, shifts cell metabolism from oxidative phosphorylation to glycolysis, which triggers excessive inflammatory responses and cytokine storms ( Mahrooz et al, 2021 ), indicating that cellular metabolism is closely linked to SARS-CoV-2 infection. LncRNA is differentially expressed in COVID-19-infected patients ( Devadoss et al, 2021 ; Taheri et al, 2021 ).…”

Section: The Relationship Between Glycolysis Lncrna and Antiviral Innate Immunitymentioning

confidence: 99%

The Triangle Relationship Between Long Noncoding RNA, RIG-I-like Receptor Signaling Pathway, and Glycolysis

Ren

Chen

et al. 2021

Front. Microbiol.

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Long noncoding RNA (LncRNA), a noncoding RNA over 200nt in length, can regulate glycolysis through metabolic pathways, glucose metabolizing enzymes, and epigenetic reprogramming. Upon viral infection, increased aerobic glycolysis providzes material and energy for viral replication. Mitochondrial antiviral signaling protein (MAVS) is the only protein-specified downstream of retinoic acid-inducible gene I (RIG-I) that bridges the gap between antiviral immunity and glycolysis. MAVS binding to RIG-I inhibits MAVS binding to Hexokinase (HK2), thereby impairing glycolysis, while excess lactate production inhibits MAVS and the downstream antiviral immune response, facilitating viral replication. LncRNAs can also regulate antiviral innate immunity by interacting with RIG-I and downstream signaling pathways and by regulating the expression of interferons and interferon-stimulated genes (ISGs). Altogether, we summarize the relationship between glycolysis, antiviral immunity, and lncRNAs and propose that lncRNAs interact with glycolysis and antiviral pathways, providing a new perspective for the future treatment against virus infection, including SARS-CoV-2.

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The complex combination of COVID-19 and diabetes: pleiotropic changes in glucose metabolism

Cited by 35 publications

References 81 publications

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

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

Hyperglycemia and Loss of Redox Homeostasis in COVID-19 Patients

The Triangle Relationship Between Long Noncoding RNA, RIG-I-like Receptor Signaling Pathway, and Glycolysis

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