Genetic abrogation of the amplifying pathway in pancreatic ß-cells: effects on diet-induced obesity

Dr. Melis Karaca is using mice to study the role of the pancreas in regulating the glucose content in blood (glycemia) and in overweight gain. Her results indicate that one specific protein, called GDH, is essential in pancreas function. She is investigating the importance of GDH regarding insulin secretion and the onset of obesity and type 2 diabetes. She aims to understand how efficient an insulin-secreting pancreatic cell should be to maintain normoglycemia and what adaptations of peripheral organs are induced by low cell efficiency.
The role of mitochondrial enzyme GDH in the pancreatic ß-cell using mice with ß-cell-specific GDH deletion (ßGlud1-/-) developed in the lab. Our results indicate that GDH is essential for the amplification of the secretory response in ß-cells. Remarkably, such limited ß-cell function, established prior to initiation of high-calorie feeding, protects against overweight gain. We will further characterize ßGlud1-/- mice and explore a new tamoxifen inducible model in the β-cell to investigate the importance of ß-cell GDH-dependent amplifying pathway in the etiology of obesity and type 2 diabetes. In particular, we aim at addressing the following questions: How efficient ß-cell should be to maintain normo-glycemia? Which adaptations of peripheral organs are induced by lower ß-cell efficiency? Is there a threshold for ß-cell efficiency necessary for maintenance of normo-glycemia?