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Abstract: TH-PO637

The Effects of Dietary Glucose on Urinary Exosomal MicroRNA Expression in an Insulin-Resistant Mouse Model

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1300 Health Maintenance, Nutrition, and Metabolism

Authors

  • Fluitt, Maurice B., Georgetown University, Washington, District of Columbia, United States
  • Ecelbarger, Carolyn M., Georgetown University, Washington, District of Columbia, United States
Background

Exosomal microRNAs provide a unique entry point to elucidate the molecular mechanisms of several metabolic processes and disease, including glucose metabolism and diabetic kidney disease. In addition, these miRNAs hold promise as attractive early non-invasive markers of disease. However, one limitation to the use of miRNAs as novel therapeutic interventions and early markers of disease is the influence of environmental and dietary factors on its expression. The goal of this study was to determine the effects of dietary glucose (ingestion) on the excretion of urinary exosomal miRNAs in an insulin-resistant mouse model.

Methods

8 TALLYHO/Jng male mice were divided into three treatment groups with normal access to normal or 10% glucose drinking water for three-weeks. 24-hour urine was collected at baseline and week 3. Urinary exosomes were isolated using commercially available miRCURY Exosome kits and confirmed by western blotting.

Results

A diabetes pathway specific miRNA array revealed that 12 UE miRNAs were differentially expressed from baseline and week-3. UE miR-34a-5p, miR-320-3p, miR-26a-5p, miR-26b-5p, miR-23a-3p, miR-21a-5p, miR-194-5p, miR-1907, miR-185-59, and miR-126a-5p were increased 2-fold or greater, while miR-361-5p and let-7e-5p were decreased 2-fold or greater from baseline to week-3 in glucose-treated mice.

Conclusion

These findings suggest that these miRNAs play important roles in regulating processes associated with the development of diabetes and its complications, including diabetic kidney disease, and have potential as early markers and therapeutic targets for improving insulin sensitivity and renal senescence.

Funding

  • Private Foundation Support