# Beta cell dysfunction as an acute and a post acute sequelae of COVID19

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2022 · $584,795

## Abstract

PROJECT SUMMARY
Beta cell dysfunction and death are significant pathologies underlying the development of Type 2 diabetes. Our
long-term goal is to identify molecular mechanisms restrict beta cell function and survival. During the SARS-
CoV2-driven COVID19 pandemic, there are reports of adult COVID19+ patients presenting with diabetic
ketoacidosis in emergency rooms. 25% of new-onset type 1 diabetes (T1D) patients presenting with diabetic
ketoacidosis in the T1D Exchange registry are COVID19+. Our group has reported a significant increase in the
number of new-onset type 2 diabetes patients presenting in diabetic ketoacidosis. This suggests that the
pathogenesis of COVID19 may have acute and specific effects on pancreatic beta cell function. One of the
barriers to understanding how SARS-CoV2 infection may affect beta cell function and survival in patients is the
limited number of physiologically relevant animal models to study. We have capitalized on unique access the
pancreas of SCV2-innoculated animals to model and understand how the infection may affect beta cell function
and survival. Our preliminary data that shows: (1) SARS-CoV2 directly infects beta cells, (2) SARS-CoV2
infection causes dramatic morphological changes in islet, (3) SARS-CoV2 infection shifts beta cell metabolism
to glycolytic profile, and (4) SARS-CoV2 infection results in decreased in beta cell function and survival.
The objective of this proposal is to define the mechanisms that drive the post-acute consequences of
COVID19-mediated beta cell injury in vivo. There is controversy in the literature regarding if SARS-CoV2
directly infects beta cells and affects beta cell function and survival or if the disruption of glucose homeostasis in
patients is secondary. We hypothesize that SARS-CoV2 infection reprograms cellular metabolism and
induces necroptosis, thus leaving hosts susceptible to beta cell dysfunction acutely and as a post-acute
sequelae of COVID19. These highly innovative experiments capitalize on a unique and clinically relevant model
system and employs cutting edge techniques to assess how beta cell survival and metabolism are affected by
SARS-CoV2 infection. These experiments will provide critical mechanistic insight to the underpinnings of the
emerging clinical phenotype of acute hyperglycemia, diabetic ketoacidosis, and potentially lifelong diabetes that
may afflict a significant number of patients who have recovered from COVID19.

## Key facts

- **NIH application ID:** 10505064
- **Project number:** 1R01DK133504-01
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Senta K Georgia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $584,795
- **Award type:** 1
- **Project period:** 2022-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10505064

## Citation

> US National Institutes of Health, RePORTER application 10505064, Beta cell dysfunction as an acute and a post acute sequelae of COVID19 (1R01DK133504-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10505064. Licensed CC0.

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