# Impact of in utero diabetes exposure on miRNA: effects on cellular metabolism

> **NIH NIH R03** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2021 · $94,500

## Abstract

Abstract
Future risk for the development of cardiometabolic disease in youth, including type 2 diabetes, is increased by
exposure to maternal diabetes (DM) in utero. These early exposures “program” the offspring toward
cardiometabolic disease. Studies from my K23 indicate that a specific miRNA, miR-126, is highly abundant in
human umbilical vein endothelial cells, placenta, and circulation, targeting elements in the insulin signaling
pathway, potentially leading to insulin resistance. However, the effects of miR-126 on cell function and
differences in mRNA targets based on cell type and diabetes exposure were not examined. My overall
hypothesis is that maternal diabetes increases miR-126 expression in the infant, and this is an important
epigenetic driver of insulin resistance and cellular metabolism. Therefore, the overarching goal of the
proposed research is to determine how miR-126 disrupts cellular metabolism in fetal cells and to discover
novel targets for these pathways. Perinatal studies of miRNA are limited in scope, with most focusing on
candidate miRNA species and their putative targets without direct testing of the mechanistic impact. The
current proposal will overcome these constraints and extend our current work by a) investigating the impact of
maternal DM on cellular function, b) examining biological effects of miR-126 at the cellular level and c)
identifying additional mRNA targets of miR-126 in a cell/context-specific fashion.
Aim 1. To test the hypothesis that maternal diabetes exposure increases miR-126 abundance altering
cellular metabolism.
Aim 2. To test the hypothesis that the targets of miR-126 will be cell-type specific and altered by DM
exposure.
We hypothesize that DM exposure will result in decreased glucose uptake and proliferation, but an increase in
senescence associated with increased abundance of miR-126; and in vitro, miR-126 will decrease glucose
uptake in the adipocytes and decrease proliferation but increase senescence in the mesenchymal stem cell
(MSC). Glucose uptake will be measured in adipocytes using glucose isotope. Proliferation will be assessed by
MTT assay, and senescence will be assessed via flow cytometry in the MSCs. miR-126 will be transfected into
the DM exposed and unexposed cells with repetition of the above studies to determine the direct effect of miR-
126. In the second aim, high-throughput sequencing of RNA by crosslinking immunoprecipitation (HITS-CLIP)
in MSCs and differentiated adipocytes exposed and unexposed to DM will identify novel targets within each
cell type as well as the impact of the DM exposure on target selection. These targets will then be examined by
Western blot analysis. Understanding the biological and metabolic pathways altered by miRNAs will further
elucidate their impact on cellular metabolism and increased risk of cardiometabolic complications, including
obesity and diabetes, in youth exposed to DM. Understanding these alterations will be key to prevention.

## Key facts

- **NIH application ID:** 10217867
- **Project number:** 1R03DK125626-01A1
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Jeanie Beatrice Tryggestad
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $94,500
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217867

## Citation

> US National Institutes of Health, RePORTER application 10217867, Impact of in utero diabetes exposure on miRNA: effects on cellular metabolism (1R03DK125626-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10217867. Licensed CC0.

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