| Summary: | ER stress is associated with beta-cell dysfunction in Type 2 diabetes (T2D). A recent
study by Dorajoo and colleagues show that several ER stress implicated genes
including HSP90B1, DNAJC3, UCHL1 are upregulated in pancreatic islets from
Singaporean-Chinese donors. Besides these genes, OLMALINC, a lincRNA with
unknown function in beta-cells, was upregulated. We thus explored the effect of
OLMALINC knockdown (KD) on expression of ER stress-related and beta-cell
signature genes, under both normal and ER stress conditions. A second gene,
ERO1β, shown to be important in mediating ER stress responses and beta-cell
function in murine cell lines and mouse models, was also studied in the context of
human beta-cells under normal and ER stress conditions. Our results show that
OLMALINC KD had no significant impact on either beta-cell function or beta-cell
responsiveness to heightened ER stress, suggesting that OLMALINC does not play
a role in ER stress or significantly impact beta-cell identity and function. In contrast,
ERO1β KD induced critical ER stress-related gene expression under ER stress
conditions, corroborating murine models that ERO1β significantly impacted beta-cells
responsiveness to ER stress. However, this effect was not seen in normal, nonER
stress conditions. Our results propose that ERO1β downregulation in beta-cells
may exacerbate ER stress, promote beta-cell dysfunction and thereby drive T2D
pathogenesis.
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