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 islet over the human lifespan. In terms of normal pancreatic islet development, we are studying the fetal human pancreas, the juvenile human pancreas (less than age 18), and the adult human pancreas. We are interested in how islet morphology, gene expression, and function change as humans age and adapt to different physiologic conditions such as puberty and insulin resistance. In addition to studying islet gene expression (hormones, key islet-enriched transcription factors, and differentiation markers), we are also studying the innervation and vascularization of islets. Islets are richly innervated and vascularized and we are interested in interactions between these processes and islet cell function.

2) Describe the features of insulin+ cells remaining in the pancreas of individuals with Type 1 diabetes (T1D). We seek to understand the functional characteristics, and molecular signatures of the insulin+ cells remaining in the pancreas of individuals with T1D. Little is known about the remaining insulin+ cells and their functional status, or how those cells have survived in the inhospitable metabolic and immunologic environment. It is not known whether these insulin+ cells are ‘normal’ β cells.

3) Describe the features of islets and beta cells in the pancreas of individuals with cystic fibrosis-related diabetes (CFRD). This form of diabetes is becoming increasingly common, but the pathogenesis is incompletely understood. By studying samples in the nPOD repository, we hope to determine how these beta cells compare to normal beta cells.

We are using or hope to use nPOD samples from both the control and diabetic pancreas. We will combine information from nPOD samples with our results from samples from human pancreatic tissues that our group has recently collected (fetal and juvenile). We will examine these tissues by immunohistochemistry and other methods such as tissue imaging mass spectrometry. We will use antibodies that are widely available and also new antibodies that are being developed by investigators in the Beta Cell Biology Consortium.

July 11, 2014