..the Diabetes Research Group at the medical center and currently also directs the Diabetes Research Center at the University of Washington. Dr. Kahn started his research career examining the relationship between insulin sensitivity of the tissues and the ability of the pancreas to release insulin. In this work he demonstrated that the interaction of these organs is governed, like most endocrine systems, by a feedback loop that is tasked with maintaining the exquisite regulation of the body’s glucose levels. His work, along with that of his colleagues, helped create a paradigm shift in the understanding of the abnormalities that lead to the development of type 2 diabetes and the high-risk condition called prediabetes. Based on their studies, it is now well accepted that the basis for the development of type 2 diabetes and for the progression of the disease is the inability of the pancreatic islet ß-cell to secrete the requisite amounts of insulin. This recognition has also resulted in approaches to the prevention and treatment of type 2 diabetes including attempts to maintain ß-cell health. Dr. Kahn currently leads two large clinical trials sponsored by NIDDK and administered by SIBCR: the Diabetes Prevention Program (DPP) and Look AHEAD. He chairs the “Restoring Insulin Secretion (RISE) Study”, a seven center NIDDK study that will launch in 2013 and will address how best to slow or prevent the relentless loss of islet ß-cell function in prediabetes or recently diagnosed type 2 diabetes. He has trained more than twenty post-doctoral fellows and it is this aspect of his work that makes him most proud. Three of them, Drs. Hull, Utzschneider and Zraika do their research at VA Puget Sound, and all have independent NIH funding. He has been elected to the American Society for Clinical Investigation and American Association of Physicians, and has received a number of prestigious awards including this year The Endocrine Society Clinical Investigator Award.

…focuses broadly on how novel aspects of the islet milieu contribute to dysfunction and death of the islet β-cell that are a critical component of diabetes pathogenesis. Her current research interests aim to answer three main questions: 1. How does the islet endothelial cell contribute to β cell failure in type 2 diabetes? Rebecca’s lab has shown that islet endothelial cells develop an infl ammatory and proadhesive phenotype in multiple models of diabetes. This is associated with altered composition and remodeling of the islet extracellular matrix. This altered endothelial phenotype results in decreased insulin release from islets, suggesting it is a novel modulator of the beta cell in diabetic conditions and thus a potential therapeutic target. She is using novel in vitro approaches, along with animal models to understand how and why the islet endothelial cell becomes dysfunctional and how this affects β cell function in diabetes. 2. What are the mechanisms underlying islet amyloid-mediated toxicity? Rebecca’s recent data suggests that islet endothelial cells are a novel target of islet amyloid toxicity (a pathological feature that occurs in almost all individuals with type 2 diabetes). Further, her work shows that islet amyloidinduced infl ammation in islet endothelial cells has numerous downstream effects that impact the β cell. Specifi cally, these include further stimulation of islet amyloid formation, recruitment and activation of macrophages and direct effects to impair β cell function and/or survival. 3. What causes islet failure in cystic fi brosis-related diabetes? Diabetes affects up to 50% of patients with cystic fi brosis, but islet pathology and the mechanisms by which islet dysfunction occur in CFRD are still poorly understood. Rebecca recently found that islet infl ammation is a widespread feature of CFRD, occurring even in young children with the disease; we are following up on those observations in the lab. Islet amyloid is also a common feature of CFRD, but it occurs decades earlier in this disease than it is typically seen in type 2 diabetes, suggesting a different etiology. Her group is studying a novel mouse model that expresses the most common human CF mutation along with amyloidogenic (human) islet amyloid polypeptide in order to better understand the role of islet amyloid in the development of CFRD