The etiology of type 1 diabetes (T1D) and type 2 diabetes (T2D) is complex with evidence suggesting that the failure of the pancreatic insulin producing β-cells is a hallmark abnormality attributing to failed regulation of hyperglycemia. The underlying mechanisms that contribute to diabetes pathogenesis, particularly how β-cells contribute to their own demise, have yet to be elucidated, which in the end can help to afford new strategies for prevention or cures.
The overall research objective in the laboratory of Naureen Javeed, Ph.D., is to exploit the idea of altered cellular communication between β-cells during the pathogenesis of diabetes through studying the exchange of secretory nanovesicles called extracellular vesicles (EVs). Secreted by all cell types, these cellular conduits reflect the state of the cell through packaging of various DNA, RNA, proteins and others. Dr. Javeed's lab investigates alterations in the molecular cargo in β-cell EVs, with the goal of identifying how EVs contribute to the overall pathogenesis of both T1D and T2D.
- Role of extracellular vesicles in the β-cell stress response in T1D. T1D is a chronic autoimmune disease that targets destruction of the β-cells, leading to hyperglycemia. Emerging evidence suggests that the β-cell is an active contributor of its own demise during the pathogenesis of T1D. The work in Dr. Javeed's laboratory is focused on understanding the physiological and molecular mechanisms of the β-cell stress response mediated by circulating EVs by using approaches to understand content and functional alterations of EVs during progressing T1D.
- Extracellular vesicles as prognostic indicators of early-onset T1D. At the time of clinical diagnosis, a substantial portion of functional beta cell mass has already been lost (70% to 80%) in T1D, thus there is a dire need for reliable biomarkers of β-cell health to monitor early-onset events, including β-cell dysfunction, which precede β-cell loss. Currently, circulating autoantibodies against β-cell autoantigens are the only predictive clinical biomarkers for T1D; however, they do not directly correlate to early-stage β-cell dysfunction and loss, but rather later-stage autoimmunity. Work in Dr. Javeed's lab focuses on determining novel early prognostic biomarkers of declining β-cell health in T1D through identification of alterations in circulating EV content.
- Elucidating the mechanisms of β-cell extracellular vesicles in the pathogenesis of T2D. Chronically elevated diabetogenic factors including circulating free fatty acids (FFA) and elevated glucose levels contribute to β-cell dysfunction and thus to the onset of obesity-driven T2D. Increasing evidence suggests that aberrant release of EVs contribute to the pathogenesis of β-cell failure in T2D. Dr. Javeed's group will explore the role of β-cell-derived EV in the pathogenesis of T2D by understanding the physiologically and mechanistic implications of altered β-cell communication to neighboring islet cells and other metabolically active tissues through the release of EVs.
Significance to patient care
The pathophysiology of diabetes is complex with evidence suggesting that pancreatic β-cell failure is a hallmark abnormality attributing to failed regulation of glucose homeostasis and hyperglycemia. The loss of functional β-cells is a key feature preceding the onset of hyperglycemia in both T1D and T2D.
To effectively combat the loss of β-cell function in diabetes, successful treatment strategies should be geared toward restoration and regeneration of appropriate β-cell functional mass through enhancement of β-cell function. Indeed, restoration of functional β-cell mass has been described as a critical barrier for successful treatment strategies to combat the rise in diabetes prevalence and consequent complications.