# The role of Nrf2 in beta cell expansion during pregnancy

> **NIH NIH K01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $131,490

## Abstract

Summary
The late stages of the mammalian pregnancy are accompanied with increased insulin resistance due to the
increased glucose demand of the growing fetus. Therefore, as a compensatory response, in order to maintain
the maternal normal blood glucose levels, the beta cells mass expands leading to increased insulin release.
Beta cell proliferation, beta cell neogenesis, and decreased beta cell apoptosis, are believed to be major
contributors for beta cell adaptive response during pregnancy and defects in this adaptive response can lead to
gestational diabetes mellitus (GDM). My preliminary results indicate that Nrf2 is required for adaptive beta cell
expansion in adult mice during overnutrition, and that Nrf2 levels are upregulated in beta cells of pregnant
mice. Despite multiple studies describing Nrf2 protective effects on beta cells in Type 2 and Type 1 diabetic
models, no study has ever uncovered the role of Nrf2 in the expansion of beta cell mass during pregnancy.
Does in vivo loss- or gain-of-Nrf2 function affect beta cell proliferation, survival and mass in pregnant mice?
Does this potential alteration persist in the early post-partum period? Does in vivo loss- or gain-of-Nrf2 function
affect insulin secretion in pregnant mice? Does in vivo loss- or gain-of-Nrf2 function affect glucose homeostasis
in pregnant mice? Which genes are upregulated and downregulated in islets during pregnancy in response to
in vivo loss or gain of Nrf2 function? Which are the Nrf2 target genes in islets during pregnancy? Do human
beta cells also require Nrf2 for pregnancy-driven proliferation? These important questions about the
physiological role of Nrf2 in beta cells during pregnancy need to be answered to advance our knowledge and
find therapeutic means to treat GDM. We hypothesize that Nrf2 is necessary for beta cell expansion during
pregnancy and that disruption of Nrf2 expression or function leads to GDM. We believe Nrf2 can serve as a
potential therapeutic target for treating GDM. We will test our hypothesis by completing the following specific
aims: 1) To determine the role of Nrf2 on the expansion of beta-cell mass during pregnancy. 2) To uncover the
mechanisms by which Nrf2 regulates beta-cell mass expansion during pregnancy. 3) To test if Nrf2 is
necessary for pregnancy-mediated adaptive human beta cell proliferation in vivo. These studies will provide
insight into how Nrf2 promotes expansion of functional beta-cell mass during pregnancy and will provide a
crucial basic platform for designing and testing novel therapeutic strategies for the treatment of GDM.

## Key facts

- **NIH application ID:** 10745306
- **Project number:** 5K01DK128387-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Sharon Alterzon
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $131,490
- **Award type:** 5
- **Project period:** 2022-02-01 → 2024-10-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10745306

## Citation

> US National Institutes of Health, RePORTER application 10745306, The role of Nrf2 in beta cell expansion during pregnancy (5K01DK128387-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10745306. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*