Endocrine Abstracts

Background and Aims: As a loss of functional β-cell mass contributes to type 2 diabetes (T2D), increasing β-cell proliferation is a potential therapy to compensate for impaired insulin output. Long non-coding RNAs (lncRNAs) regulate several key β-cell genes and the presence of more than 1100 human β-cell enriched lncRNAs raises the potential for wider roles. Here we have identified 5 independent studies that capture the β-cell transcriptome during adaptive and maladaptive changes to proliferation in human and mouse and bio informatically investigate lncRNAs with potential roles in β-cell expansion.

Methods: Islet and β-cell RNA-Seq datasets were selected from Gene Expression Omnibus to cover a range of conditions that affect β-cell proliferation. These included pregnancy, dietary or monogenic models of obesity, glucose tolerance (GT) and development. Reads were mapped using Hisat2 and quantified with FeatureCounts. Differential expression analysis was performed using DESeq2 and gene lists were filtered using Ensembl biotypes to identify lncRNAs.

Results: Differentially-expressed (DE) lncRNAs were identified in each study with padj <0.1 as shown below.

Conclusions: Hundreds of lncRNAs were identified across a range of conditions influencing proliferation in β-cell studies in human and mouse. Patterns observed between these lists could provide insight into undiscovered players involved in core β-cell proliferation pathways.