Role of free fatty acid signaling in islet function

E Lorza-Gil; GKH Przemeck; ER Ulven; S Sabrautzki; M Panse; F Gerst; HU Häring; T Ulven; M Hrabě de Angelis; S Ullrich

doi:10.1055/s-0038-1641773

Diabetologie und Stoffwechsel, Inhaltsverzeichnis

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

¹Universitätsklinikum Tübingen, Institut für Diabetes Forschung und Metabolische Krankheiten des Helmholtz Zentrum München an der Universität Tübingen (IDM), Department für Pathophysiologie des Prediabetes, Tübingen, Germany

²German Center for Diabetes Research (DZD e.V.), Tübingen, Germany

,

GKH Przemeck

³Helmholtz Zentrum München, Institute of Experimental Genetics and the German Mouse Clinic, Neuherberg, Germany

⁴German Center for Diabetes Research (DZD e.V.), München, Germany

,

ER Ulven

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

,

S Sabrautzki

³Helmholtz Zentrum München, Institute of Experimental Genetics and the German Mouse Clinic, Neuherberg, Germany

⁶Helmholtz Zentrum München, Research Unit Comparative Medicine, Neuherberg, Germany

,

M Panse

²German Center for Diabetes Research (DZD e.V.), Tübingen, Germany

⁷University Hospital Tübingen, Internal Medicine IV, Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, Tübingen, Germany

,

F Gerst

²German Center for Diabetes Research (DZD e.V.), Tübingen, Germany

⁸Institute 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

²German Center for Diabetes Research (DZD e.V.), Tübingen, Germany

⁹University Hospital Tübingen, Internal Medicine IV, Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, Tübingen, Germany

,

T Ulven

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

,

M Hrabě de Angelis

³Helmholtz Zentrum München, Institute of Experimental Genetics and the German Mouse Clinic, Neuherberg, Germany

¹¹Technische Universität München, Chair of Experimental Genetics, School of Life Sciences Weihenstephan, München, Germany

,

S Ullrich

²German Center for Diabetes Research (DZD e.V.), Tübingen, Germany

⁸Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tübingen (IDM), Department für Pathophysiologie des Prediabetes, Tübingen, Germany

› Institutsangaben

Abstract

Volltext

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.