Dental Tribune India

COVID-19 can lead to diabetes mellitus

By Rajeev Chitguppi, Dental Tribune South Asia
June 13, 2021

So far, the COVID-19 management has mainly focused on pneumonia and blood clots. Now evidence is building up on how COVID-19 recovered individuals can develop diabetes mellitus.

Earlier lab studies had suggested that the COVID-19 virus SARS-CoV-2 can infect beta cells of the pancreas - the insulin-producing cells of the human body. [1] 

Beta cells and other cell types in the pancreas express the viral entry proteins - the Angiotensin-Converting Enzyme- 2 (ACE2) receptor protein, the Transmembrane Serine Protease 2 (TMPRSS2), and Neuropilin 1 (NRP1) - all of which are needed for SARS-CoV-2 to enter and infect human cells. Once inside the cells, the virus replicates to generate multiple copies. [2]

Once infected, β-cells will show morphological changes - reduced numbers of insulin-secretory granules; and functional changes - impaired glucose-stimulated insulin secretion. These early studies suggest that the human pancreas could be a target of SARS-CoV-2 infection and that β-cell infection could contribute to the metabolic dysregulation observed in patients with COVID-19. Even the autopsy studies done on the pancreatic tissue showed that SARS-CoV-2 might preferentially infect the insulin-producing β-cells. [3]

Two new studies, supported by the National Institute of Health (NIH), have shown that SARS-CoV-2 can target the pancreas and impair the function of insulin-producing beta cells, leading to insulin insufficiency and diabetes mellitus. [4, 5]

SARS-CoV-2 infection can directly cause the death of some of the pancreatic β-cells [4], while the remaining β-cells that survive undergo transdifferentiation and get reprogrammed [5].

The net result is that the pancreatic cells start producing less insulin, which leads to less utilization of glucose. It also results in more glucagon production leading to the breakdown of liver glycogen, raising the glucose levels further. [2]

Do we have any possible interventions here? Yes! 

Death of β-cells from infection can be prevented by blocking NRP1. [4]

The process of β-cell transdifferentiation can be reversed by an Integrated Stress Response (ISR) Inhibitor (trans-ISRIB), which reduces the cellular stress response. [5]

References:

[1] A human pluripotent stem cell-based platform to study SARS-CoV-2 tropism and model virus infection in human cells and organoids. Yang L, Han Y, Nilsson-Payant BE, Evans T, Schwartz RE, Chen S, et al. Cell Stem Cell. 2020 Jul 2;27(1):125-136.e7.

[2] How COVID-19 Can Lead to Diabetes. NIH Director’s Blog.  https://directorsblog.nih.gov/2021/06/08/how-covid-19-can-lead-to-diabetes/ [Accessed June 13, 2021]

[3] SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Müller JA, Groß R, Conzelmann C, Münch J, Heller S, Kleger A, et al. Nat Metab. 2021 Feb;3(2):149-165.

[4] SARS-CoV-2 infects human pancreatic beta cells and elicits beta-cell impairment. Wu et al. Cell Metab. 2021 May 18; S1550-4131(21)00230-8.

[5] SARS-CoV-2 infection induces beta-cell transdifferentiation. Tang et al. Cell Metab 2021 May 19; S1550-4131(21)00232-1.

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