Identification of a unique transcriptomic signature associated with islet amyloidosis

Abstract

AbstractAimsThis cross-sectional study aims to identify potential transcriptomic changes conveyed by presence of amyloid deposits in islets from pancreatic tissue obtained from metabolically profiled living donors.MethodsAfter establishing Thioflavin S as the most sensitive approach to detect islet amyloid plaques, we utilized RNA sequencing data obtained from laser capture microdissected islets to define transcriptomic effects of this pathological entity. The RNA sequencing data was used to identify differentially expressed genes by linear modeling. Further analyses included functional enrichment analysis of KEGG and Hallmark gene sets as well as a weighted gene correlation network analysis.ResultsEleven differentially expressed genes were identified in islets affected by amyloidosis. Enrichment analyses pointed to signatures related to protein aggregation diseases, energy metabolism and inflammatory response. A gene co-expression module was identified that correlated to islet amyloidosis.ConclusionAlthough the influence of underlying Type 2 diabetes could not be entirely excluded, this study presents a valuable insight into the biology of islet amyloidosis, particularly providing hints into the potential relationship between islet amyloid deposition and structural and functional proteins involved in insulin secretion.Research in contextWhat is already known about this subject?Islet amyloidosis is the only histological marker of Type 2 diabetes in the pancreasIndividuals not suffering from Type 2 diabetes can also be affected by islet amyloidosisThe clinicopathological significance of this phenomenon is still unclearWhat is the key question?Does the islet transcriptome of individuals with islet amyloidosis provide explanations for the onset of this phenomenon and its pathophysiological value?What are the new findings?Islet transcriptomes of affected subjects exhibit only limited transcriptomic differences compared to unaffected ones.Structural and functional proteins involved in insulin secretion machinery may be involved in the pathophysiological sequence of amyloid formation