Beta Cell Physiology and Pathology
Group Leaders are Drs. Franz Matschinsky, Ali Naji and Klaus KaestnerThis Scientific focus area of the DERC is linked to the IDOM Type 1 Diabetes Unit
The beta cell has long been the focus of research in type 1 diabetes. More recently it has become accepted that abnormal beta cell function is critical to the development of type 2 diabetes as well. This topic includes strength in beta cell biology per se as well as complementary expertise in beta cell immunology and islet/pancreas transplantation.
Highlights of Significant Findings
This area has long been strength of the Penn DERC, and during the past funding period Penn DERC investigators have made major contributions to the understanding of beta cell physiology and pathophysiology, which includes the areas of insulin gene expression, insulin secretion, and beta cell immunology. One particular highlight has been the collaborative work in hyperinsulinism. Interactions between Drs. Stanley, Kaestner, and Matschinsky are a wonderful example of the convergence of basic and clinical investigation, and how the Penn DERC facilitates communication and collaboration in this context.
Dr. Kaestner’s finding of an exciting mouse model of hyperinsulinism hypoglycemia benefited from Dr. Stanley’s dissections of the genetic basis of congenital hyperinsulinism in humans; most recently, Dr. Stanley's group has reciprocally created a mouse model of the human syndrome. Another highlight has been Dr. Birnbaum's application of his insights into Akt and PI3-kinase signaling pathways to beta cell function, which was catalyzed by the resources and expertise in this focus area. Further, DERC pilot funding has enabled two new DERC investigators, Drs. Stoffers and Rulifson, to make major contributions. Dr. Stoffers discovered a regulator of the critical b -cell transcription factor Pdx1, while Rulifson has taken advantage of the power of fly genetics and his own creative approaches to discover the neuronal origin of cells that make the insulin-like metabolic regulator in Drosophila.
DERC investigators have also stepped up efforts in patient-oriented investigation using the GCRC and the Rodebaugh Clinical Diabetes Center. Highlights include the first physiological studies of hormone secretion and glucose metabolism from islets after transplant. These were made possible by collaborations among the surgeons, an outstanding new translational investigator funded by a DERC pilot and feasibility grant (Dr. Rickels), and Dr. Teff, the DERC's Assistant Director for Translational Research.