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20-HETE promotes glucose-stimulated insulin secretion in an autocrine manner through FFAR1

Author

Listed:
  • Sorin Tunaru

    (Department of Pharmacology)

  • Remy Bonnavion

    (Department of Pharmacology)

  • Isabell Brandenburger

    (Department of Pharmacology)

  • Jens Preussner

    (Max Planck Institute for Heart and Lung Research)

  • Dominique Thomas

    (Klinikum der Goethe-Universität Frankfurt)

  • Klaus Scholich

    (Klinikum der Goethe-Universität Frankfurt)

  • Stefan Offermanns

    (Department of Pharmacology
    J.W. Goethe University Frankfurt)

Abstract

The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic β-cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote glucose-stimulated insulin secretion (GSIS). However, the physiological role of FFAR1 in β-cells remains poorly understood. Here we show that 20-HETE activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than dietary fatty acids such as palmitic, linoleic, and α-linolenic acid. Murine and human β-cells produce 20-HETE, and the ω-hydroxylase-mediated formation and release of 20-HETE is strongly stimulated by glucose. Pharmacological inhibition of 20-HETE formation and blockade of FFAR1 in islets inhibits GSIS. In islets from type-2 diabetic humans and mice, glucose-stimulated 20-HETE formation and 20-HETE-dependent stimulation of GSIS are strongly reduced. We show that 20-HETE is an FFAR1 agonist, which functions as an autocrine positive feed-forward regulator of GSIS, and that a reduced glucose-induced 20-HETE formation contributes to inefficient GSIS in type-2 diabetes.

Suggested Citation

  • Sorin Tunaru & Remy Bonnavion & Isabell Brandenburger & Jens Preussner & Dominique Thomas & Klaus Scholich & Stefan Offermanns, 2018. "20-HETE promotes glucose-stimulated insulin secretion in an autocrine manner through FFAR1," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02539-4
    DOI: 10.1038/s41467-017-02539-4
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