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How SARS-CoV-2 Infection Causes Diabetes

Type 1 diabetes occurs when beta cells in the pancreas fail to synthesize enough insulin to metabolize glucose, leading to hyperglycemia. Some people develop diabetes after an acute COVID-19 infection. Some recent research has begun to elucidate the mechanisms by which infection with SARS-CoV-2 can cause diabetes.

Earlier laboratory studies had shown that the insulin producing beta cells in the pancreas express the ACE2 receptor protein, the TMPRSS2 enzyme protein, and neuropilin 1 (NRP1), which are needed for SARS-CoV-2 to enter and infect human cells. Once SARS-CoV-2 infects beta cells, it can replicate and spread to other cells.

Two new studies, published as pre-prints in the journal Cell Metabolism, have shed more light on how SARS-CoV-2 can cause diabetes. Both studies confirmed infection of pancreatic beta cells in autopsy tissue from people who died of COVID-19. These studies also showed that SARS-CoV-2 infection of beta cells reduced production and secretion of insulin from pancreatic islets. Infected beta cells went through a process of transdifferentiation in which they were reprogrammed to produce less insulin and more glucagon. The latter hormone promotes the breakdown of glycogen into glucose. Transdifferentiation worsens insulin deficiency and raises blood glucose levels.

References: How COVID-19 can lead to diabetes, Francis Collins, NIH Director’s Blog, June 8th, 2021.

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

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.

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.

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.

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