Differential transcriptome analysis of diabetes resistant and sensitive mouse islets reveals significant overlap with human diabetes susceptibility genes
- Oliver Kluth1,3,
- Daniela Matzke1,3,
- Gunnar Schulze1,3,
- Robert W. Schwenk1,3,
- Hans-Georg Joost2,3 and
- Annette Schürmann1⇑
- 1Department of Experimental Diabetology
- 2Department of Pharmacology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany
- 3German Center for Diabetes Research, Neuherberg, Germany
- Corresponding Author: A. Schürmann, E-mail:
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.
- © 2014 by the American Diabetes Association.
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