PT  - JOURNAL ARTICLE
AU  - Barovic, Marko
AU  - Steinmeyer, Klaus
AU  - Kipke, Nicole
AU  - Schöniger, Eyke
AU  - Friedland, Daniela
AU  - Marzetta, Flavia
AU  - Forberger, Almuth
AU  - Baretton, Gustavo
AU  - Weitz, Jürgen
AU  - Aust, Daniela
AU  - Ibberson, Mark
AU  - Distler, Marius
AU  - Schulte, Anke M
AU  - Solimena, Michele
TI  - Identification of a unique transcriptomic signature associated with islet amyloidosis
AID  - 10.1101/2022.11.09.515784
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.11.09.515784
4099  - http://biorxiv.org/content/early/2022/11/10/2022.11.09.515784.short
4100  - http://biorxiv.org/content/early/2022/11/10/2022.11.09.515784.full
AB  - Aims This 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.Methods After 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.Results Eleven 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.Conclusion Although 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.What 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 formationCompeting Interest StatementThe authors have declared no competing interest.