Methylglyoxal in COVID-19-induced hyperglycemia and new-onset diabetes.
Eur Rev Med Pharmacol Sci
; 26(21): 8152-8171, 2022 Nov.
Article
in English
| MEDLINE | ID: covidwho-2249211
ABSTRACT
Elevation in blood glucose is common in COVID-19 patients. There is also a high incidence of new-onset diabetes mellitus (DM) in COVID-19 patients following hospitalization. To date, the underlying cause(s) for the hyperglycemia and new-onset DM post-COVID-19 remain poorly understood. In this narrative review, we suggest that upregulation of the cytotoxic and diffusible glycolytic byproduct methylglyoxal (MGO) arising from increased glycolysis in infected pancreatic islets, macrophages, and peripheral cells/tissues is impairing insulin production, secretion, and signaling. This hypothesis is based on our recent discovery that MGO levels were elevated in the plasma of hospitalized COVID-19 patients without and with DM and even higher in COVID-19 patients that succumb to the disease. In pancreatic islets infected with SARS-CoV-2, elevated MGO will disrupt mitochondrial function, perturb Ca2+ homeostasis, and activate the receptors for advanced glycation end-product (RAGE) and nuclear factor kappa B (NF-kB) resulting in impaired insulin production and secretion. In macrophages, excess MG production can diffuse into the vasculature disrupting endothelial function and triggering micro/macro hemorrhage, ischemia, and tissue fibrosis. In skeletal muscle and liver cells, MGO disruption of insulin signaling can blunt glucose absorption. Metformin and N-acetyl cysteine have recently been shown to decrease morbidity and mortality in COVID-19 patients. Here we propose that these agents may be exerting their beneficial effects by chemically reacting with and lowering MGO levels. Knowledge gained from this review should provide novel mechanistic insights for hyperglycemia in COVID-19 patients and strategies to blunt the development of new-onset of DM in post-COVID patients.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Diabetes Mellitus
/
COVID-19
/
Hyperglycemia
Type of study:
Observational study
/
Reviews
Topics:
Long Covid
Limits:
Humans
Language:
English
Journal:
Eur Rev Med Pharmacol Sci
Journal subject:
Pharmacology
/
Toxicology
Year:
2022
Document Type:
Article
Affiliation country:
Eurrev_202211_30169
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