Insight into Islet Pathology in Type 2 Diabetes

Webinar: Quantitative Analysis of Pancreas Immunostaining – Insight into Islet Pathology in Type 2 Diabetes

Speaker: Rebecca Hull, PhD, University of Washington

Thursday, April 18, 2013

View webinar here


Type 2 diabetes is characterized by loss of ?-cell mass and function. Islet amyloid deposition occurs in the vast majority subjects with type 2 diabetes. The extent of islet amyloid deposition is associated with decreased islet ?-cell area and increased ?-cell apoptosis, suggesting that islet amyloid contributes to ?-cell loss. To better understand the detrimental effects of amyloid deposition in islets, we developed a transgenic mouse model that expresses the human, amyloidogenic form of islet amyloid polypeptide (hIAPP) in its ? cells. In vivo studies demonstrated that increased dietary fat intake increases islet amyloid deposition in these mice, resulting in ?-cell loss. Anti-diabetic therapies, including rosiglitazone and metformin are highly effective in inhibiting islet amyloid deposition and its detrimental effects on the ? cell. Islet transplantation is another setting in which amyloid deposition likely has detrimental effects. Indeed, transplantation of hIAPP transgenic islets into diabetic mice results in amyloid deposition, leading to increased ?-cell apoptosis, with no corresponding increase in ?-cell replication and ultimately leading to ?-cell loss. Amyloid deposition can also be induced in isolated islets from these mice, with culture at elevated glucose levels. This in vitro model has allowed us to demonstrate roles for oxidative stress and JNK signaling, but not ER stress, in mediating amyloid-induced ?-cell apoptosis. Recently, we have been working to identify strategies to inhibit islet amyloid deposition, with the goal of developing novel therapeutic strategies to limit amyloid-induced ?-cell loss in diabetes.

About our Speaker

Dr. Rebecca L. Hull received her PhD in Biochemistry from the University of Nottingham, and undertook her postdoctoral training at the University of Washington prior to joining the faculty there.  Her research focuses on the mechanisms of pancreatic islet b-cell failure in type 2 diabetes. Dr. Hull is currently a Research Associate Professor in the Division of Metabolism, Endocrinology and Nutrition at the Veterans Affairs Puget Sound Health Care System and University of Washington School of Medicine.  She is Associate Director of the University of Washington Diabetes Research Center’s Cellular and Molecular Imaging Core and is an editorial board member for the Journal of Histochemistry and Cytochemistry. She has extensive expertise in specimen collection and immunostaining in pancreas, cultured islets and islet transplant grafts from humans and rodents.  She has expertise in morphometric analysis and has used these data to obtain sensitive measures of beta-cell mass, replication and apoptosis, and amyloid deposition for many of her studies.