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

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
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Publikationsverlauf

Publikationsdatum:
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.