# β cell miRNAs Function as Molecular Hubs of Type 1 Diabetes Pathogenesis

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $40,874

## Abstract

ABSTRACT: Gestational diabetes mellitus (GDM) is a heterogenous disease that is defined by the occurrence
of glucose intolerance or hyperglycemia during the late second trimester and occurs when pancreatic β cells
cannot secrete sufficient insulin when there is increasing insulin resistance. GDM affects approximately 10% of
all pregnancies and negatively impacts the short-and long-term health of both pregnant mothers and their
offspring. microRNAs (miRNAs, 18-25 nt) are a class of small non-coding RNAs that post transcriptionally
modulate gene expression and have been shown to regulate several key processes within the β cell. miRNAs
have also been implicated as potential biomarkers for type 1 diabetes, and type 2 diabetes. Past studies have
also demonstrated a potential for miRNAs to serve as biomarkers for GDM as well, but most only employed
targeted approaches and did not consider the contribution of maternal overweight/obesity. Against this
background, we obtained plasma samples collected from pregnant mothers enrolled in the Nulliparous
Pregnancy Outcomes Study-Monitoring Mothers-to-be (nuMoM2b; NCT01322529) study to perform unbiased
miRNA sequencing. Our preliminary data showed that maternal overweight/obesity status (defined as BMI≥25)
influenced plasma miRNA signatures. Compared to controls in the same BMI category, we identified a set of
miRNAs that were different in pregnant mothers who subsequently developed GDM. This result indicates the
potential of miRNA signatures to predict GDM onset prior to onset of hyperglycemia. Interestingly, we also
found that miR-517a-3p, a placental-enriched miRNA that is known to increase cellular proliferation, was
downregulated in mothers who subsequently developed GDM. In Aim 1, we hypothesize that the upregulation
of miR-517a-3p positively regulates β cell function and survival. To test this hypothesis, we will define the
unreported role of miR-517a-3p in regulating β cell function using INS-1 cells, murine islets, and human islet
models, as well as using state-of-the-art RNA-seq approach to uncover the modulated genes and molecular
pathways. In Aim 2, we hypothesize that a combination of miRNA signatures and clinical variables will improve
the prediction of GDM. This hypothesis will be tested by quantifying the expression levels of these miRNA
signatures using expanded sample sets from the multi-center nuMoM2b study and analyzed using appropriate
model-selection methods in collaboration with Dr. Joanne Daggy (IU Dept of Biostatistics and Health Data
Science). This R01 supplement will also support time for the candidate (Dr. Kua) to perform experiments and
attend training courses to acquire new research skills to pursue a career as an independent physician scientist.
The candidate training will include three main objectives: (1) Obtain state-of-the-art training in miRNA biology
and their role in modulating β cell function and gestational diabetes risk, (2) develop experimental toolkits to
support trans...

## Key facts

- **NIH application ID:** 10561855
- **Project number:** 3R01DK127308-02S1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Carmella Evans-Molina
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $40,874
- **Award type:** 3
- **Project period:** 2022-07-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10561855

## Citation

> US National Institutes of Health, RePORTER application 10561855, β cell miRNAs Function as Molecular Hubs of Type 1 Diabetes Pathogenesis (3R01DK127308-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10561855. Licensed CC0.

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