Circular RNAs are an emerging new class of non-coding RNA molecule with gene regulatory potential; dysregulation of circRNAs has been reported in association with several human diseases. Here we aimed to produce an enriched circRNA profile for human pancreatic islets, and explore the relationship between circRNA expression, diabetes status, genotype at T2D risk loci and measures of glycaemia (insulin secretory index; SI and HbA1c) in human islet preparations from healthy control donors and donors with type 2 diabetes. We also assessed the effect of elevated glucose, cytokine and lipid and hypoxia on circRNA expression in the human beta cell line Endo-BetaH1. We identified over 2600 circRNAs present in islets, of which 47 had not been previously described in other tissues. Of the five most abundant circRNA in human islets, four (circCIRBP, circZKSCAN, circRPH3AL and circCAMSAP1) demonstrated marked associations with diabetes status. CircCIRBP also demonstrated an association with insulin secretory index in isolated human islets and circCIRBP and circRPH3AL displayed altered expression with elevated fatty acid in treated Endo-BetaH1 cells. CircCAMSAP1 was also noted to be associated with T2D status in human peripheral blood. No associations between circRNA expression and genotype at T2D risk loci were identified in our samples. Our data suggest that circRNA are abundantly expressed in human islets, are differentially regulated in the islets of donors with type 2 diabetes, and some may derive from genes with roles in exocytosis or stress resilience.
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