Differential transcriptome analysis of diabetes resistant and sensitive mouse islets reveals significant overlap with human diabetes susceptibility genes

  1. Annette Schürmann1
  1. 1Department of Experimental Diabetology
  2. 2Department of Pharmacology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany
  3. 3German Center for Diabetes Research, Neuherberg, Germany
  1. Corresponding Author: A. Schürmann, E-mail: schuermann{at}dife.de

Abstract

Type 2 diabetes in humans and in obese mice is polygenic. In recent genome-wide association studies (GWAS) genetic markers explaining small portion of the genetic contribution to the disease were discovered. However, functional evidence linking these genes with the pathogenesis of diabetes is scarce. We have performed RNA-sequencing based transcriptomics of islets from two obese mice, a diabetes-susceptible (NZO) and a diabetes-resistant (B6-ob/ob) mouse after a short glucose challenge in order to compare these results with human data. Aligning 2328 differentially expressed genes to 106 human diabetes candidate genes revealed an overlap of 20 genes, including TCF7L2, IGFBP2, CDKN2A, CDKN2B, GRB10 and PRC1. Our data provide a functional validation of human diabetes candidate genes including those involved in regulating islet cell recovery and proliferation, and identify additional candidates that could be involved in human beta-cell failure.

  • Received March 14, 2014.
  • Accepted July 10, 2014.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.