Browsing by Author "Dhawan, Sangeeta"

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    Cyclin D2 is sufficient to drive β cell self-renewal and regeneration
    (Taylor & Francis, 2017-11-03) Tschen, Shuen-ing; Zeng, Chun; Field, Loren; Dhawan, Sangeeta; Bhushan, Anil; Georgia, Senta; Medicine, School of Medicine
    Diabetes results from an inadequate mass of functional β cells, due to either β cell loss caused by autoimmune destruction (type I diabetes) or β cell failure in response to insulin resistance (type II diabetes). Elucidating the mechanisms that regulate β cell mass may be key to developing new techniques that foster β cell regeneration as a cellular therapy to treat diabetes. While previous studies concluded that cyclin D2 is required for postnatal β cell self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive β cell self-renewal. Using transgenic mice that overexpress cyclin D2 specifically in β cells, we show that cyclin D2 overexpression increases β cell self-renewal post-weaning and results in increased β cell mass. β cells that overexpress cyclin D2 are responsive to glucose stimulation, suggesting they are functionally mature. β cells that overexpress cyclin D2 demonstrate an enhanced regenerative capacity after injury induced by streptozotocin toxicity. To understand if cyclin D2 overexpression is sufficient to drive β cell self-renewal, we generated a novel mouse model where cyclin D2 is only expressed in β cells of cyclin D2−/− mice. Transgenic overexpression of cyclin D2 in cyclin D2−/− β cells was sufficient to restore β cell mass, maintain normoglycaemia, and improve regenerative capacity when compared with cyclin D2−/− littermates. Taken together, our results indicate that cyclin D2 is sufficient to regulate β cell self-renewal and that manipulation of its expression could be used to enhance β cell regeneration.
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    The Yin and Yang of Modulating β-Cell DNA Damage Response and Functional Mass
    (American Diabetes Association, 2022) Spaeth, Jason M.; Dhawan, Sangeeta; Biochemistry and Molecular Biology, School of Medicine