The prevalence of type 1 diabetes (T1D) is on the rise, posing a significant burden on healthcare systems. T1D results from the immune system mistakenly attacking insulin–producing pancreatic β–cells, necessitating lifelong insulin treatment and continuous monitoring of blood sugar levels. The complex inflammatory nature of T1D, coupled with substantial gaps in our understanding of the […]
Category: Beta Cell Physiology and Dysfunction
Defining the link between Islet prohormone accumulation and secretion in type 1 diabetes
An improved understanding of the pathophysiologic mechanisms contributing to insulin deficiency in type 1 diabetes (T1D) is crucial to optimize approaches to disease prevention and treatment. Multiple groups have described increases in beta cell prohormones in individuals at different stages of T1D development, both at the level of the islet and in circulation. These findings […]
Investigating the role of iron metabolism in beta cell function and the immunopathology of type 1 diabetes
Insulin release from beta cells depends on ATP energy generated by mitochondrial. The electron transport chain is the primary group of proteins that make ATP energy and they require iron to do so. Consequently, iron is essential for insulin release, and iron deficiency inhibits beta cell function. Conversely, excess cellular iron leads to an increase […]
Uridine in the pathogenesis of T1D
Blood uridine levels are elevated in T1D. However, its significance to the disease pathogenesis remains largely unexplored. Our pilot studies indicate uridine regulates glucose–stimulated insulin secretion (GSIS) in mouse and human islets. We will use human pancreas tissue sections and live pancreas slices to study how chronic elevation in blood uridine might affect beta cell […]
Leveraging heterogeneity to identify markers of resilient β-cells in T1D
We aim to identify factors contributing to the destruction ofβ–cells in diabetes. In this project, we took advantage of publicly available bulk and single cell gene expression datasets from human islets of healthy and diabetic donors(T1D and T2D). We used deep transfer learning platform DEGAS1 combinedwith this data to identify subsets of β–cells within human […]
Immediate-early gene transcription factor (IEG-TF) expression within human pancreatic islets during pregnancy and gestational diabetes
Pregnancy is a unique physiologic state in adult females that occurs and resolves over a defined time period. The acute metabolic stress it causes on the mother triggers adaptations with maternal pancreatic islets. Failure of normal islet adaptation is a major contributor to gestational diabetes (GDM).In rodents, insulin-producing beta-cells proliferate causing expansion of beta-cell mass. […]
The insulin secretory granule components and its immune recognition in type 1 diabetes
Our parent project studies the intracellular accumulation and molecular interaction of proinsulin, insulin and the proinsulin processing enzymes PC1/3, PC2 and CPE, which may be dysregulated during the development of the disease and lead to processing errors. Our interest was focused on proinsulin and insulin, as these are the most abundant molecules of the insulin […]
Spatio-temporal visualization of immune and non-immune islet injury in Type 1 Diabetes
Type 1 Diabetes (T1D) generally results from a poorly understood autoimmune process that leads to selective destruction of pancreatic beta cells. Interestingly, beta cell function is often not correlated with mass and declines very early in the disease before symptom onset, but the mechanisms driving this are not known. Islet beta cells existing in a […]