Diabetologie und Stoffwechsel 2022; 17(S 01): S54
DOI: 10.1055/s-0042-1746357
Abstracts | DDG
02. Poster

Identification and functional investigation of novel candidate genes for type 2 diabetes on chromosome 4

Authors

  • Katharina Kaiser

    1   German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Düsseldorf, Germany, Institute for Clinical Biochemistry and Pathobiochemistry, Düsseldorf, Germany

  • Sarah Görigk

    2   German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Düsseldorf, Germany, Institute for Clinical Biochemistry and Pathobiochemistry, Duesseldorf, Germany

  • Jasmine Decker

    2   German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Düsseldorf, Germany, Institute for Clinical Biochemistry and Pathobiochemistry, Duesseldorf, Germany

  • Delsi Altenhofen

    2   German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Düsseldorf, Germany, Institute for Clinical Biochemistry and Pathobiochemistry, Duesseldorf, Germany

  • Sandra Lebek

    2   German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Düsseldorf, Germany, Institute for Clinical Biochemistry and Pathobiochemistry, Duesseldorf, Germany

  • Tanja Kuhn

    2   German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Düsseldorf, Germany, Institute for Clinical Biochemistry and Pathobiochemistry, Duesseldorf, Germany

  • Alexandra Chadt

    2   German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Düsseldorf, Germany, Institute for Clinical Biochemistry and Pathobiochemistry, Duesseldorf, Germany

  • Hadi Al-Hasani

    2   German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Düsseldorf, Germany, Institute for Clinical Biochemistry and Pathobiochemistry, Duesseldorf, Germany
Further Information
Also available at
 
 

    Background and aims Individual susceptibility for type 2 diabetes is strongly determined by genetic variants, many of them still unknown. Crossbreeding of the diabetes-susceptible NZO strain with mice from the lean, diabetes-resistant 129/P2 strain revealed a novel diabetes risk locus (QTL) on chromosome 4 (Nbg4) linked to elevated blood glucose, plasma insulin and liver weight. Our aim is to identify the causal genes for Nbg4 and their molecular function.

    Methods Candidate genes in adipose tissue were selected by expression profiling using microarrays to include Ptpn3 (protein tyrosine phosphatase, non-receptor type 3), Rad23b (RAD23 homolog B, nucleotide excision repair protein), AI314180 (Ecm29 proteasome adaptor and scaffold), Svep1 (sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1) and Alad (aminolevulinate, delta-, dehydratase). To understand their specific role in blood glucose control, insulin-stimulated glucose uptake, Oil Red O staining and quantitative Real-time PCR were conducted after knockdown or overexpression of the respective gene in 3T3-L1 adipocytes.

    Results Si-RNA mediated knockdown of Alad in 3T3-L1 adipocytes resulted in reduced insulin-stimulated glucose uptake. The knockdown of Svep1 led to a significantly altered expression of several genes associated with lipolysis, including Atgl. Knockdown of Rad23b and AI314180 had no influence on glucose uptake and lipid metabolism in 3T3-L1 adipocytes.

    Conclusion Data from our experiments indicated a possible role of Alad and Svep1 in glucose and lipid metabolism in adipocytes. Both genes constitute novel candidates for diabetes-related traits and further experiments will determine their molecular function in fat cells in more detail.


     

    Interessenkonflikt

    Es besteht kein Interessenskonflikt.

    Publication History

    Article published online:
    26 May 2022

    © 2022. Thieme. All rights reserved.

    Georg Thieme Verlag KG
    Rüdigerstraße 14, 70469 Stuttgart, Germany