Investigating the role of TGIF in beta cell function and diabetes
Abstract
Diabetes mellitus is a devastating metabolic disease characterized by hyperglycemia that can occur through distinct mechanisms, such as Beta-cell destruction, Beta-cell failure, and insulin resistance in peripheral tissues. The increasing prevalence of diabetes also affects the military personnel. Several genes associated with diabetes have been identified in genome wide association studies, but their genetic validation as causative factors remains largely unexplored. In this grant proposal, we focused on one of these genes, TGIF, whose conditional overexpression in the pancreatic tissue led to severe hyperglycemia and diabetes. We proposed experiments to investigate how TGIF induces diabetes. The results showed that conditional overexpression of TGIF in pancreatic progenitor cells in mice resulted in diabetes by decreasing insulin production by islet Beta-cells. Mechanistic experiments demonstrate that TGIF suppresses insulin production by directly repressing the expression ofPdx1, the master transcription factor in b-cell, which drives expression of insulin. Loss-of-function genetic experiments demonstrated that TGIF plays an instrumental role in diabetes associated with obesity, thereby implicating TGIF as a possible target for attenuating diabetes in obese patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2020
- Accession Number
- AD1097373
Entities
People
- Yin-Yuan Mo
Organizations
- University of Mississippi Medical Center