title: Differential transcriptome analysis of diabetes-resistant and -sensitive mouse islets reveals significant overlap with human diabetes susceptibility genes.
abstract: Type 2 diabetes in humans and in obese mice is polygenic. In recent genome-wide association studies, genetic markers explaining a 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 performed RNA sequencing-based transcriptomics of islets from two obese mouse strains, a diabetes-susceptible (NZO) and a diabetes-resistant (B6-ob/ob) mouse, after a short glucose challenge and compared these results with human data. Alignment of 2,328 differentially expressed genes to 106 human diabetes candidate genes revealed an overlap of 20 genes, including TCF7L2, IGFBP2, CDKN2A, CDKN2B, GRB10, and PRC1. The 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 β-cell failure.
authors: Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany German Center for Diabetes Research, Neuherberg, Germany.
authors: Oliver
authors: O
authors: Kluth
authors: Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany German Center for Diabetes Research, Neuherberg, Germany.
authors: Daniela
authors: D
authors: Matzke
authors: Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany German Center for Diabetes Research, Neuherberg, Germany.
authors: Gunnar
authors: G
authors: Schulze
authors: Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany German Center for Diabetes Research, Neuherberg, Germany.
authors: Robert W
authors: RW
authors: Schwenk
authors: German Center for Diabetes Research, Neuherberg, Germany Department of Pharmacology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany.
authors: Hans-Georg
authors: HG
authors: Joost
authors: Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany schuermann@dife.de.
authors: Annette
authors: A
authors: Schürmann
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D051383:GRB10 Adaptor Protein / Q000235:genetics; D020869:Gene Expression Profiling; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009765:Obesity / Q000150:complications / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D018971:Insulin-Like Growth Factor Binding Protein 2; D058118:Transcription Factor 7-Like 2 Protein; D051383:GRB10 Adaptor Protein