RNA-Seq to identify genes expressed by islets in response to metabolic and inflammatory stress and the role of CN/NFAT signaling in this response

To identify genes expressed in islets in response to metabolic and inflammatory stress, we performed total RNA-Seq on isolated human islets exposed to IL-1ß in the presence of high glucose. Gene ontology (GO) analysis of upregulated transcripts indicated enrichment of genes associated with cytokine signaling and proinflammatory responses. Multiple cytokines and chemokines were induced, and several key regulators of oxidative and ER stress responses were upregulated. The results revealed acute induction of proinflammatory transcripts and upregulation of genes involved in oxidative and ER stress in human islets in response to IL-1ß and high glucose. Blockade of CN/NFAT signaling by FK506 pretreatment resulted in suppression of genes required for islet cell differentiation, development, and function. Overall design: Islets from a human donor were collected and experimental treatments done in duplicate. Treatment samples were normalized to the untreated control samples.