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ER Stress and ATF6alpha potently induce S-Phase in Old Mouse Beta Cells Cultured Ex-Vivo in High Glucose

Snyder, Jarin T.
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Student Authors
Faculty Advisor
Laura Alonso
Academic Program
Interdisciplinary Graduate Program
UMass Chan Affiliations
Document Type
Master's Thesis
Publication Date
2020-12-11
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Abstract

Aging is associated with a loss of proliferation of the insulin-secreting beta cell, a possible contributing factor to the greatly increased rate of type-2 diabetes in the elderly. A landmark study from our lab previously illustrated that mild endoplasmic reticulum (ER) stress drives beta cell proliferation specifically through ATF6α, one arm of the tripartite Unfolded Protein Response (UPR). It is unknown if old beta cells differ from young beta cells in UPR signaling or proliferative response to ER stress or ATF6α activation. To investigate, young and old mouse islets were cultured ex vivo in high glucose, and beta cell proliferation was quantified by BrdU incorporation after treatment with low dose thapsigargin or activation of overexpressed ATF6α. In addition, levels of UPR signaling were compared by semi-quantitative Xbp1 splicing assay. Interestingly, although old beta cells displayed reduced proliferation in glucose compared to young beta cells, their proliferative response to low-dose thapsigargin and ATF6α activation were nearly identical, and no difference was found in Xbp1 splicing under high glucose or high ER stress conditions. These results suggest that the aged mouse beta cell does not have impaired UPR-responsive proliferation or aberrant UPR signaling when cultured ex vivo

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DOI
10.13028/97hs-zs51
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