Email this page

Print this page

Research Paper

Identification of genes selectively disallowed in the pancreatic islet

Timothy J. Pullen, Arshad M. Khan, Geraint Barton, Sarah A. Butcher, Gao Sun and Guy A. Rutter

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.

We have previously identified two genes, encoding lactate dehydrogenase (Ldha) and the monocarboxylate carrier, MCT1 (Slc16a1) whose expression is remarkably low in pancreatic β-cells and islets. We sought here to determine whether these may be part of a larger family of genes selectively repressed (“disallowed”) in the pancreatic islet. Using new and publicly available microarray data, we undertook a bioinformatic analysis of gene expression in islets and a range of other murine tissues. We compared data sets from three sources of mouse pancreatic islets with a total of 30 datasets from nine tissues, to identify genes with at least five-fold down-regulation in islets. 39 genes were revealed as being specifically repressed in islets. These included Ldha and Slc16a1 as expected but also genes involved in several other metabolic pathways which could affect glucose stimulated insulin secretion. Of these, adenylate kinase 3 (AK3) is a mitochondrial enzyme which acts on GTP, and ornithine aminotransferase (OAT) lies on the pathway converting glutamate to ornithine. The removal of an enzyme which could dissipate mitochondrial GTP levels in beta cells provides support for the theory that mitochondrial GTP may be an important for regulating insulin secretion, whilst blocking an alternative metabolic fate for glutamate is consistent with a signalling role for glutamate. The identification of these genes should inform efforts to generate fully functional β-cells from stem cell sources, and may provide new targets in type 2 diabetes.

Authors

Timothy J. Pullen

Section of Cell Biology, Division of Medicine, Imperial College, London, UK

Arshad M. Khan

Centre for Bioinformatics, Division of Molecular Biosciences, Imperial College, London, UK

Geraint Barton

Centre for Bioinformatics, Division of Molecular Biosciences, Imperial College, London, UK

Sarah A. Butcher

Centre for Bioinformatics, Division of Molecular Biosciences, Imperial College, London, UK

Gao Sun

Section of Cell Biology, Division of Medicine, Imperial College, London, UK

Guy A. Rutter

Section of Cell Biology, Division of Medicine, Imperial College, London, UK

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.