Islet Gene View-a tool to facilitate islet research.

Area of Science:

• Endocrinology
• Genomics
• Molecular Biology

Background:

• Understanding gene expression in pancreatic islets is crucial for type 2 diabetes (T2D) research.
• Alterations in islet gene expression contribute to T2D pathogenesis.

Purpose of the Study:

• To create an accessible platform, the Islet Gene View (IGW), for exploring islet gene expression data.
• To identify differentially expressed genes (DEGs) in T2D islets and their relationship with islet function and phenotypes.

Main Methods:

• RNA sequencing and genome-wide genotyping were performed on islets from 188 donors.
• The IGW web application was developed to visualize and analyze gene expression data.
• Differential gene expression analysis was conducted comparing T2D and control islets.

Main Results:

• The IGW platform identified 284 DEGs in T2D islets compared to controls.
• Forty percent of DEGs showed cell-type enrichment and significant co-expression with islet hormone genes (GCG, IAPP, INS, SST).
• Inhibition of UNC5D and SERPINE2 (DEGs) impaired glucose-stimulated insulin secretion and beta-cell survival in a human model.

Conclusions:

• The IGW platform provides a valuable resource for the scientific community to study islet gene expression in T2D.
• Identified DEGs like UNC5D and SERPINE2 represent potential therapeutic targets for T2D.
• Further functional studies using IGW data can advance our understanding of T2D pathogenesis.