Diabetes and susceptibility to infections: Implication for COVID-19.
Immunology
; 164(3): 467-475, 2021 11.
Article
in English
| MEDLINE | ID: covidwho-1266332
ABSTRACT
A number of mechanisms have been proposed to explain the well-established link between diabetic status and an increased susceptibility to infection. Notably, diabetes has been shown to be one of the strongest factors influencing healthcare outcome in COVID-19 infections. Though it has long been noted that lymphocytes upregulate insulin receptors following immune activation, until recently, this observation has received little attention. Here, we point out key findings implicating dysregulated insulin signalling in immune cells as a possible contributing factor in the immune pathology associated with diabetes. Mechanistically, insulin, by activating the PI3K/Akt/mTOR pathway, regulates various aspects of both myeloid cells and lymphocytes, such as cell survival, metabolic reprogramming and the polarization and differentiation of immune cells. PI3K signalling is also supressed by immune checkpoint proteins, suggesting that insulin signalling may antagonize peripheral tolerance. Remarkably, it has also recently been shown that, following insulin binding, the insulin receptor translocates to the nucleus where it plays a key role in regulating the transcription of various immune-related genes, including pathways involved in viral infections. Taken together, these observations suggest that dysregulated insulin signalling may directly contribute to a defective immune response during COVID-19 infections.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Blood Glucose
/
Lymphocytes
/
Diabetes Mellitus, Type 1
/
SARS-CoV-2
/
COVID-19
/
Insulin
Type of study:
Observational study
/
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Immunology
Year:
2021
Document Type:
Article
Affiliation country:
Imm.13383
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