# Placental Hormones and O-GlcNAcylation in Gestational Diabetes

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2022 · $364,177

## Abstract

PROJECT SUMMARY/ ABSTRACT
Every year, about 18 million babies are born from mothers with gestational diabetes mellitus (GDM).
While diabetic symptoms usually resolve after delivery, lasting complications can occur for both mother
and child, including fetal overgrowth, type 2 diabetes (T2D), cardiovascular diseases, and obesity.
While pathologically similar to type 2 diabetes, the rapidity of progression of GDM is unique to
pregnancy, and likely arises from placental dysfunction. Increased blood glucose availability in a
healthy pregnancy is vital for proper fetal development. A surge of placental hormones initiates a state
of mild insulin resistance, which, combined with beta-cell dysfunction, likely causes GDM. Currently,
effective treatments for GDM are limited or unsafe. Thus, an in-depth understanding of the
pathophysiology of GDM becomes essential to prevent GDM and design innovative, non-toxic, and
highly effective GDM treatments. Our research program aims to investigate GDM development by
studying for the first time the role of nutrient-dependent O-GlcNAcylation on placental endocrine
function. Directly dependent on plasma glucose levels, intracellular O-GlcNAcylation is a common
dynamic post-translational modification that impacts numerous signaling pathways and diseases.
Based on literature and preliminary data, we gathered that O-GlcNAcylation affects classical hormonal
secretion (in non-pregnant animals), is critical for placental physiology, and impairs insulin signaling.
Thus, we hypothesize that O-GlcNAcylation-dependent hormonal changes partly drive GDM. First, we
will define the involvement of O-GlcNAcylated protein in physiological placenta endocrine secretion
and, second, assess whether O-GlcNAc deregulations lead to GDM. We hope to propose novel
molecular targets and signaling pathways involved in placental physiology and disease and advance
the prevention and treatment of pregnancy metabolic diseases.

## Key facts

- **NIH application ID:** 10363426
- **Project number:** 1R01HD104808-01A1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Stephanie Olivier-Van Stichelen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $364,177
- **Award type:** 1
- **Project period:** 2022-08-26 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10363426

## Citation

> US National Institutes of Health, RePORTER application 10363426, Placental Hormones and O-GlcNAcylation in Gestational Diabetes (1R01HD104808-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10363426. Licensed CC0.

---

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