A role of glycation and methylation for SARS-CoV-2 infection in diabetes?
Copyright © 2020 Elsevier Ltd. All rights reserved..
Type-2 diabetes (T2D) is a major comorbidity of COVID-19, and poorly controlled diabetes is associated with high mortality rate, emphasizing the necessity to improve glycemic control. Angiotensin-converting enzyme 2 (ACE2) is the receptor responsible for SARS-CoV-2 access to human cells, and ACE2 expression is increased in patients with diabetes and hypertension treated with ACE-inhibitors or angiotensin II receptor blockers. We hypothesize that an upregulation of ACE2 due to its non-enzymatic glycation could be considered, as well as a change of the protein tertiary structure in terms of amino acid (mostly lysine) available to be glycated. In fact, in a single ACE2 molecule, 34 lysine residues are present in the extracellular portion, and at least one of these is co-involved in a fundamental hydrogen-bond interaction with the SARS-CoV-2 receptor binding domain (RBD). The worse outcome of COVID-19 in people with diabetes could be related to the non-enzymatic glycation that triggers the activity of ACE2. Moreover, DNA methylation of genes regulating islet beta-cell function, as well as in insulin resistance of peripheral tissues such as liver, muscle, and adipose tissue may be involved, as already demonstrated for cancer conditions. DNA methylation, besides being considered as a biomarker to predict the risk of obesity and T2D, has been suggested also as a target for dietary and pharmacological treatments. The present observations may suggest further interventions in order to improve the outcome of COVID-19 in people affected by diabetes.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:144 |
|---|---|
| Enthalten in: |
Medical hypotheses - 144(2020) vom: 01. Nov., Seite 110247 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sartore, Giovanni [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
ACE2 |
|---|
| Anmerkungen: |
Date Completed 04.01.2021 Date Revised 04.01.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.mehy.2020.110247 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM318209179 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM318209179 | ||
| 003 | DE-627 | ||
| 005 | 20231225164855.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.mehy.2020.110247 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1060.xml |
| 035 | |a (DE-627)NLM318209179 | ||
| 035 | |a (NLM)33254553 | ||
| 035 | |a (PII)S0306-9877(20)32498-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sartore, Giovanni |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A role of glycation and methylation for SARS-CoV-2 infection in diabetes? |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.01.2021 | ||
| 500 | |a Date Revised 04.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Type-2 diabetes (T2D) is a major comorbidity of COVID-19, and poorly controlled diabetes is associated with high mortality rate, emphasizing the necessity to improve glycemic control. Angiotensin-converting enzyme 2 (ACE2) is the receptor responsible for SARS-CoV-2 access to human cells, and ACE2 expression is increased in patients with diabetes and hypertension treated with ACE-inhibitors or angiotensin II receptor blockers. We hypothesize that an upregulation of ACE2 due to its non-enzymatic glycation could be considered, as well as a change of the protein tertiary structure in terms of amino acid (mostly lysine) available to be glycated. In fact, in a single ACE2 molecule, 34 lysine residues are present in the extracellular portion, and at least one of these is co-involved in a fundamental hydrogen-bond interaction with the SARS-CoV-2 receptor binding domain (RBD). The worse outcome of COVID-19 in people with diabetes could be related to the non-enzymatic glycation that triggers the activity of ACE2. Moreover, DNA methylation of genes regulating islet beta-cell function, as well as in insulin resistance of peripheral tissues such as liver, muscle, and adipose tissue may be involved, as already demonstrated for cancer conditions. DNA methylation, besides being considered as a biomarker to predict the risk of obesity and T2D, has been suggested also as a target for dietary and pharmacological treatments. The present observations may suggest further interventions in order to improve the outcome of COVID-19 in people affected by diabetes | ||
| 650 | 4 | |a Letter | |
| 650 | 4 | |a ACE2 | |
| 650 | 4 | |a Diabetes | |
| 650 | 4 | |a Glycation | |
| 650 | 4 | |a Methylation | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a ACE2 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 650 | 7 | |a Angiotensin-Converting Enzyme 2 |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 700 | 1 | |a Ragazzi, Eugenio |e verfasserin |4 aut | |
| 700 | 1 | |a Faccin, Luca |e verfasserin |4 aut | |
| 700 | 1 | |a Lapolla, Annunziata |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Medical hypotheses |d 1983 |g 144(2020) vom: 01. Nov., Seite 110247 |w (DE-627)NLM00007487X |x 1532-2777 |7 nnns |
| 773 | 1 | 8 | |g volume:144 |g year:2020 |g day:01 |g month:11 |g pages:110247 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.mehy.2020.110247 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 144 |j 2020 |b 01 |c 11 |h 110247 | ||