Ohio State University, Columbus

The Link Between Diabetes and ACE2

A main feature of symptomatic COVID-19 disease is respiratory infection. Severe damage to the lungs during respiratory distress may cause pulmonary fibrosis, necessitating lung transplants. Lasting damages to the lungs may occur even in recovering patients with mild infections. SARS-CoV-2 targets the following cell types:

- Type I pneumocytes (AT1) 
- Type II pneumocytes (AT2) 
- alveolar macrophages

ACE2 expression is primarily seen in AT2 cells which have been shown to be involved in the reproduction and transmission of the virus.  Viral targeting of alveolar macrophages is evidenced by N antigen expression.

Effects of COVID-19 on the Lungs

Pal, R., & Bhansali, A. (2020). COVID-19, diabetes mellitus and ACE2: The conundrum. Diabetes research and clinical practice, 162, 108132. https://doi.org/10.1016/j.diabres.2020.108132

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118535/

COVID-19, diabetes mellitus and ACE2: The conundrum

- ACE2,or angiotensin-converting enzyme 2, is a protein on the surface of pneumocyte cells that assists with transport of proteins through the membrane
- Diabetes causes the ACE2 protein to under perform as well as for there to be less total
- Because of this, many diabetes medications increase the activity rate of ACE2
- These drugs stimulate ACE2 so much that the protein will sometimes let other things through that it is not supposed to, this includes SARS-CoV-2
- This accounts for the increased risk of COVID in diabetes mellitus patients
- Some drugs which have been identified to have this effect are pioglitazone and liraglutide in animal studies

Figure: How SARS-CoV-2 Enters Pneumocytes Through ACE2

Figure 1
- Alveoli are part of the lungs
- CO2 goes into the alveoli and oxygen leaves the alveoli and enters the pulmonary vein
- Due to COVID-19, immune cells are activated in the alveoli
- Epithelial cells become infected
- Inflammation is prevented
- Cytokine and chemokine are released into the pulmonary vein
- However, a cytokine storm indicates severe cases of COVID-19
- In severe cases of COVID-19, inflammation occurs → ARDS, organ failure, etc.


Pulmonary Alveoli and its Physiology in Relation to COVID-19

- Pulmonary fibrosis has been found in the autopsies of severe COVID-19 patients
- It is possible that the cytokine storm can result in pulmonary fibrosis
- Antifibrotic therapy can be useful in identifying COVID-19 patients that are on the verge of developing pulmonary fibrosis
- Nintedanib therapy prevents to formation of fibrinogen in the lungs (pirfenidone could potentially have the same effects)
- IPF results in damage to alveoli in the lungs


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