Diabetologie und Stoffwechsel 2018; 13(S 01): S6
DOI: 10.1055/s-0038-1641773
Freie Vorträge
Freie Vorträge Endokrines Pankreas
Georg Thieme Verlag KG Stuttgart · New York

Role of free fatty acid signaling in islet function

Authors

  • E Lorza-Gil

    1   Universitätsklinikum Tübingen, Institut für Diabetes Forschung und Metabolische Krankheiten des Helmholtz Zentrum München an der Universität Tübingen (IDM), Department für Pathophysiologie des Prediabetes, Tübingen, Germany
    2   German Center for Diabetes Research (DZD e.V.), Tübingen, Germany

  • GKH Przemeck

    3   Helmholtz Zentrum München, Institute of Experimental Genetics and the German Mouse Clinic, Neuherberg, Germany
    4   German Center for Diabetes Research (DZD e.V.), München, Germany

  • ER Ulven

    5   University of Southern Denmark, Department of Physics, Chemistry and Pharmacy, Odense M, Denmark

  • S Sabrautzki

    3   Helmholtz Zentrum München, Institute of Experimental Genetics and the German Mouse Clinic, Neuherberg, Germany
    6   Helmholtz Zentrum München, Research Unit Comparative Medicine, Neuherberg, Germany

  • M Panse

    2   German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
    7   University Hospital Tübingen, Internal Medicine IV, Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, Tübingen, Germany

  • F Gerst

    2   German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
    8   Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tübingen (IDM), Department für Pathophysiologie des Prediabetes, Tübingen, Germany

  • HU Häring

    2   German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
    9   University Hospital Tübingen, Internal Medicine IV, Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, Tübingen, Germany

  • T Ulven

    10   University of Copenhagen, Department of Drug Design and Pharmacology, Copenhagen, Denmark

  • M Hrabě de Angelis

    3   Helmholtz Zentrum München, Institute of Experimental Genetics and the German Mouse Clinic, Neuherberg, Germany
    11   Technische Universität München, Chair of Experimental Genetics, School of Life Sciences Weihenstephan, München, Germany

  • S Ullrich

    2   German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
    8   Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tübingen (IDM), Department für Pathophysiologie des Prediabetes, Tübingen, Germany
Further Information

Publication History

Publication Date:
26 April 2018 (online)

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Introduction:

Acute exposure of islets to long chain fatty acids amplifies glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells through activation of the free fatty acid receptor 1 (FFAR1). In accordance, palmitate-induced secretion was largely reduced in islets of Ffar1 -/- mice and of mice carrying the mutation R258W in Ffar1 gene. Glucose tolerance, however, was impaired in Ffar1 -/- mice but improved in R258W mutant mice. In Ffar1 -/- mouse islets, the mRNA level of Ffar3 was reduced. Ffar3 and Ffar2 are short chain fatty acid receptors (SCFA). Their function in beta-cells is still controversial. Here we examined the expression and role of Ffar2 and Ffar3 in beta-cells.

Materials and methods:

The mRNA levels of islets from Ffar1 R258W/R258W, Ffar1 -/- and the respective wild-type littermates were quantified by RT-PCR. RIP-Cre-mT/mG-mice were used to analyze receptor expression in FACS-sorted beta-cells. Glucose-, SCFA- and synthetic FFAR3 agonists (1-MCPC and cpd816)- dependent insulin secretion of isolated mouse islets was assessed in static incubations.

Results:

C57/BL6N and C3HeB/FeJ mouse islets expressed comparable levels of Ffar1, Ffar2, Ffar3 and Gpr119 mRNA. Ffar4 mRNA level was at the detection limit. Ffar1 and Ffar3 mRNAs were enriched 2 – 3-fold in sorted beta-cells compared to non-beta-cells whereas Ffar2 mRNA level did not differ significantly. In sorted beta-cells of Ffar1 -/- mice, the Ffar3 mRNA level was reduced by 80% compared to wild-type beta-cells. Neither SCFA nor FFAR3-agonists affected GSIS.

Conclusion:

These observations suggest that the complete deletion of the Ffar1 gene affected the transcript level of the neighboring Ffar3 in beta-cells of Ffar1 -/- mice.