Discipline: Biological Sciences
Subcategory: Physiology and Health
Destiny Mitchell - Mississippi Valley State University
Co-Author(s): Romain Harmancey, University of Mississippi Medical Center, Jackson, MS
The prevalence of diabetes in the United States has reached epidemic proportions. While both hyperglycemia and diabetes are risk factors for heart disease, hyperglycemia has been proven to be an independent risk factor for heart disease. Recent studies have shown mechanisms by which high glucose levels modulate expression of genes in insulin sensitive tissues, such as the liver, however all mechanisms by which hyperglycemia alter gene activity in the heart are not fully understood. Our research investigates the molecular mechanisms by which nutrient oversupply causes irregular dysfunction in the heart. The strategy used in this research is based on specific genes affected by dietary manipulations in rodents. Information presented in this study investigates those genes specifically affected by glucose in the rodent heart. The identified genes were then targeted in vivo and in vitro. Heart tissue samples were collected at various time points and perfused for 60 minutes with either 25mM of glucose or 25 mM of mannitol, which was the control of this experiment. A microarray analysis was performed, identifying those genes upregulated by glucose. The results identified two genes, Txnip and nuclear receptor, Nr4a2. In order to confirm the results from the in vitro experiment, glucose and insulin challenges were performed. The result from this experiment showed cardiac expression of NR4a2 mRNA levels being quickly upregulated in response to increased blood glucose levels as well as in response to insulin treatment. Also, the increase in mRNA levels was followed by an increase in protein levels. Future experiments will aim to identify the gene targets of NR4A2 in the heart, and to determine the effect of hyperglycemia on its regulatory program.
Funder Acknowledgement(s): I thank Dr. Merry Lindsey for help in the field. I also thank Kayla Watts and Ahmed Bux for their help. Funding was provided by NIH R25 HL121042, R00 HL112952.
Faculty Advisor: Rachel Beecham,