Beta Cell Physiology and Pathology
Group Leaders are Drs. and Klaus Kaestner, Franz Matschinsky, and Ali Naji
This Scientific focus area of the DRC is linked to the IDOM Type 1 Diabetes Unit.
Beta cell failure is the hallmark of type 1 diabetes and is also critical to the development of type 2 diabetes. Studies of beta cell function have long been a major strength of the Penn DRC. More recently it has been generally accepted that abnormal beta cell function is This topic includes strength in beta cell biology per se as well as complementary expertise in b-cell immunology and islet/pancreas transplantation.
Highlights From 2006-Present:
Penn DRC investigators have made major contributions to the understanding of beta cell physiology and pathophysiology, which includes the areas of beta cell development gene expression, insulin secretion, and immunology. The Transgenic and Chimeric Mouse, Islet Cell Biology, Mouse Phenotyping, Physiology, and Metabolism, Functional Genomics, and RIA/Biomarker Cores have been essential for this body of work, and will allow future exploitation and understanding of these models which teach us how beta cells develop, function, and die.
Highlight one: Collaborative work in hyperinsulinism. Interactions between Drs. De Leon, Li, Simmons, Stanley, Stoffers, and Matschinsky are a wonderful example of the convergence of basic and clinical investigation, and how the Penn DRC facilitates communication and collaboration in this context. Dr. Stanley's group has uncovered several novel mutations leading to hyperinsulinemic hypoglycemia (e.g., Li, JBC 2010). These patients have been carefully phenotyped (e.g., Hoe J Ped 2006; Pinney, JCI 2008; Sayed Diabetes 2009) and their diseases have been translated into mouse models where novel therapies can be tested (De Leon JBC 2008). Dr. De Leon received a DRC pilot grant during the current grant cycle.
Highlight two: Pancreatic development. A large number of major contributions related to the development of the adult pancreas have been made by Drs. Kaesnter, Kushner, May, Stoffers, and Zaret (Gupta Genes Dev 2007; Teta Dev Cell 2007; Gao Genes Dev 2008; Oliver-Krasinski JCI 2009; Wandzioch Science 2009; Liu JBC 2011). Dr. May was a recipient of a DRC pilot award during the last grant period.
Highlight three: Islet immunology and transplantation. Dr. Chen has identified a novel regulator of Toll signaling, which has been implicated in insulin resistance, (Sun Cell 2008), and Dr. Naji has translated basic immunological advances into potential anti-rejection therapies in non-human primates (Liu Nature Medicine 2007). Clinical investigation by Drs. Rickels, Teff, and Naji has provided novel insights into the physiology and properties of transplanted islets (e.g., Rickels JCEM 2006, 2009, 2010).