Project Grant R01DK143607

This Project Grant, awarded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), supports basic and translational research investigating the epigenetic mechanisms of glucocorticoid action on pancreatic beta cells. The $807,446 award to Mayo Clinic Arizona, effective February 1, 2026, through January 31, 2031, will fund a comprehensive research initiative employing transcriptional, epigenetic, and multi-omic analyses to elucidate how glucocorticoid receptors regulate beta cell function and gene expression. The research encompasses three primary aims: investigating chromatin remodeling and de novo enhancer creation in beta cells; utilizing beta cell-specific knockout models to determine glucocorticoid receptor regulation of circadian islet function; and exploring how chronic glucocorticoid exposure induces beta cell dedifferentiation and dysfunction in both mouse and human models.

The deliverables from this award will advance understanding of glucocorticoid physiology and pathophysiology in pancreatic islet function, with potential applications to diabetes prevention and treatment. Research outputs will include characterization of glucocorticoid receptor-mediated chromatin remodeling mechanisms, identification of circadian integration pathways in islet homeostasis, and mechanistic models of glucocorticoid-induced beta cell failure relevant to stress-induced hyperglycemia and steroid-induced diabetes. These research products support the NIDDK program objective to promote extramural biomedical research improving understanding of disease mechanisms and leading to improved prevention, diagnosis, and treatment of diabetes and related metabolic disorders.