Category: Beta Cell Physiology and Dysfunction

In humans, GAD65 is one of the first targets of autoimmunity and 70-80% of human diabetics have antibodies against this protein. In late-onset patients, circulating GAD65 autoantibodies may even be more predicative of future disease onset than antibodies to insulin. The early appearance of GAD65 antibodies may hold a clue that GAD65 is implicated during […]

We have developed novel methods for proteomic study of beta-cells within native islets. Using antibodies to proinsulin or insulin we reported the first Biosynthetic Interaction Network for insulin (Pottekat, Cell Reports, 2013). Based upon our finding that many proteins which interact directly with insulin are T1D GWAS candidates or proteins required for ER homeostasis, we […]

The cellular processes giving rise to type 1 diabetes (T1D) and type 2 diabetes (T2D) involve the activation of inflammation, which leads to the eventual death of islet β cells.  An urgent priority in diabetes research is the discovery of biomarkers (simple blood tests) that can assist in the identification of persons at-risk for disease […]

The goal of this project is to obtain transcriptome data from human islets using either hybridization arrays or RNA sequencing technology.  We plan to obtain complete information about relative expression of all genes in islets from a number of different organ donor groups with an emphasis on: 1) donors with no autoantibodies or diabetes, 2) […]

Our project seeks to understand the molecular basis for beta cell failure in human diabetes. We have discovered that excessive glucose metabolism in beta cells may lead to double strand breaks in the DNA and activation of the tumor suppressor gene p53. With the help of nPOD, we are studying the significance if this response […]

     Our proposed studies will address a major gap in the understanding of T1D, namely, to identify the mechanisms of beta cell failure from a metabolic as well as an immunological perspective. This specific project has high potential to reveal significant, novel, and translatable information regarding beta cell dysfunction that will be of therapeutic benefit for […]

Our group is interested in pancreatic islet development and function and how beta cells are affected in diabetes. Critical discoveries from nPOD samples and resources are changing our understanding of type 1 diabetes. We are using or hope to use nPOD samples for the following studies:  1) Define and describe the normal human pancreas and […]

Heparan sulfate (HS) is a sulfated glycosaminoglycan that consists of repeating disaccharides (composed of uronic acid and glucosamine), forming a linear polysaccharide. The HS chains are assembled onto the core proteins of heparan sulfate proteoglycans (HSPGs). We recently reported that HS is localized in the peri-islet basement membrane (BM) in mice and is intensely expressed […]

The endoplasmic reticulum (ER) is an organelle that is responsible for the proper folding of proteins and biosynthesis of lipids and steroids. Disruption of ER homeostasis leads to ER stress and activates a highly conserved adaptive network called the unfolded protein response (UPR). ER stress has been implicated in several diseases associated with protein folding […]

Enteroviral infections are associated with an increased risk to develop type 1 diabetes. Several stains of enteroviruses are able to infect beta cells leading to both inflammation and cell death, two major factors for the onset of type 1 diabetes (T1D).  The cellular factors that modulate cellular permissiveness to enteroviral infection and beta cell death […]