Browsing by Author "Aguirre, Rebecca S."

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    Extracellular vesicles in β cell biology: Role of lipids in vesicle biogenesis, cargo, and intercellular signaling
    (Elsevier, 2022) Aguirre, Rebecca S.; Kulkarni, Abhishek; Becker, Matthew W.; Lei, Xiaoyong; Sarkar, Soumyadeep; Ramanadham, Sasanka; Phelps, Edward A.; Nakayasu, Ernesto S.; Sims, Emily K.; Mirmira, Raghavendra G.; Pediatrics, School of Medicine
    Background: Type 1 diabetes (T1D) is a complex autoimmune disorder whose pathogenesis involves an intricate interplay between β cells of the pancreatic islet, other islet cells, and cells of the immune system. Direct intercellular communication within the islet occurs via cell surface proteins and indirect intercellular communication has traditionally been seen as occurring via secreted proteins (e.g., endocrine hormones and cytokines). However, recent literature suggests that extracellular vesicles (EVs) secreted by β cells constitute an additional and biologically important mechanism for transmitting signals to within the islet. Scope of review: This review summarizes the general mechanisms of EV formation, with a particular focus on how lipids and lipid signaling pathways influence their formation and cargo. We review the implications of EV release from β cells for T1D pathogenesis, how EVs and their cargo might be leveraged as biomarkers of this process, and how EVs might be engineered as a therapeutic candidate to counter T1D outcomes. Major conclusions: Islet β cells have been viewed as initiators and propagators of the cellular circuit giving rise to autoimmunity in T1D. In this context, emerging literature suggests that EVs may represent a conduit for communication that holds more comprehensive messaging about the β cells from which they arise. As the field of EV biology advances, it opens the possibility that intervening with EV formation and cargo loading could be a novel disease-modifying approach in T1D.
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    Methods for Measuring Risk for Type 2 Diabetes in Youth: the Oral Glucose Tolerance Test (OGTT)
    (Springer, 2018-08) Chen, Melinda E.; Aguirre, Rebecca S.; Hannon, Tamara S.; Pediatrics, School of Medicine
    Purpose of Review The oral glucose tolerance test (OGTT) is used both in clinical practice and research to assess glucose tolerance. In addition, the OGTT is utilized for surrogate measures of insulin sensitivity and the insulin response to enteral glucose and has been widely applied in the evaluation of β-cell dysfunction in obesity, prediabetes, and type 2 diabetes. Here we review the use of the OGTT and the OGTT-derived indices for measurement of risk markers for type 2 diabetes in youth. Recent Findings Advantages of using the OGTT for measures of diabetes risk include its accessibility and the incorporation of physiological contributions of the gut-pancreas axis in the measures of insulin response to glucose. Mathematical modeling expands the potential gains from the OGTT in physiology and clinical research. Disadvantages include individual differences in the rate of glucose absorption that modify insulin responses, imperfect control of the glycemic stimulus, and poor intraindividual reproducibility. Summary Available research suggests the OGTT provides valuable information about the development of impaired glycemic control and β-cell function in obese youth along the spectrum of glucose tolerance.