Islet Gene View - a tool to facilitate islet research

Abstract

Changes in the hormone producing pancreatic islet cells are culprits in the development of diabetes, and these changes are often reflected by changes in expression of key genes. Analysis of such changes require advanced bioinformatics tools that can translate the process into simple visible information.To achieve these goals we have developed a tool called Islet Gene View (IGW), that aims to make information on gene expression in human pancreatic islets from organ donors easily accessible to the scientific community. Islet Gene View currently consists of information on islets from 188 donors where data on RNA expression of more than 15 000 genes can be related to phenotypic information (gender, age, BMI, HbA1c, insulin and glucagon secretion etc.). Also this information can be related to expression other genes and how gene expression is regulated by genetic variants(so called eQTLs, expression Quantitative Traits) The data will be accessible thorugh the easy-to-use Islet Gene View web application.2 Significance StatementWe present Islet Gene View (IGW), a web resource that aims to make information on gene expression in human pancreatic islets from organ donors easily accessible to the scientific community. In IGW, we leveraged global RNA expression data from 191 donor-islets to understand their relationship with islet phenotypes such as gender, age, BMI, HbA1c, insulin and glucagon secretion as well as with islet hormones coding genes. GWAS based on European studies have shown that 403 genetic variants associate with T2D risk however the target genes and function in islets are largely unknown. We linked T2D risk variants to gene expression in islets and further functionally report if their expression is modulated in relation to T2D status and other related features.3

Ribosomal biogenesis regulator DIMT1 controls β-cell protein synthesis, mitochondrial function, and insulin secretion

“…Given that DIMT1 is a homolog of TFB1M, a methyltransferase implicated in mitochondrial function and T2D, we mined our human islet RNA sequencing database (20). We found that DIMT1 is expressed in human islets of Langerhans; its expression was significantly increased in T2D (Figure 1A).…”

“…All other chemicals were from Sigma Aldrich. RNA sequencing of human islets was performed on 155 non-diabetic and 33 T2D islet donors (20). Human islets were acquired from a collaboration with the Nordic Network of Clinical Islet Transplantation, Uppsala, Sweden.…”

Molecular and functional profiling of human islets: from heterogeneity to human phenotypes

“…These reveal important insights into islet gene regulation (as previously reviewed [7]) and make important contributions to understanding the impact of islet-localised genetic signals on in vivo glycaemic traits [9], but no programme has yet released data on the combined molecular and functional profiling of a large number of human islet preparations. 'Islet Gene View', developed by the Excellence of Diabetes (EXODIAB) research group in Sweden and described in a recent preprint [6], may fill this gap once it is made publicly available, by connecting genetic variation, transcript expression and insulin responses in samples from 188 donors.…”

“…Although the factors driving heterogeneity at these levels remain to be fully elucidated, it is likely they are determined, at least in part, by the underlying 'molecular phenotypes' of these individuals, islets and cells. Genetic variation can now be linked to insulin secretory responses in individuals [5] and to the secretory responses of isolated islets [6]. Extensive genomic phenotyping of human islets and single cells promises to unravel relevant regulatory and pathophysiological mechanisms, and this has been recently reviewed [7].…”

Association of Single Nucleotide Polymorphisms With Insulin Secretion, Insulin Sensitivity, and Diabetes in Women With a History of Gestational Diabetes Mellitus

“…Polymorphisms associated with disposition index, HOMA-IR, or T2D were assessed for association with gene expression in human pancreatic islets in RNA-Seq data of 191 donors [24]. The data are uploaded to EGA (https://ega-archive.org/) with the following accession numbers: RNAseq: EGAS00001004042, GWAS: EGAS00001004044, and Phenotype: EGAS00001004056.…”