20-HETE promotes glucose-stimulated insulin secretion in an autocrine manner through FFAR1
- 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.
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| Author: | Sorin TunaruORCiDGND, Remy Bonnavion, Isabell BrandenburgerGND, Jens PreussnerORCiDGND, Dominique Jeanette ThomasORCiDGND, Klaus ScholichORCiD, Stefan OffermannsORCiDGND |
|---|---|
| URN: | urn:nbn:de:hebis:30:3-458238 |
| DOI: | https://doi.org/10.1038/s41467-017-02539-4 |
| ISSN: | 2041-1723 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/29330456 |
| Parent Title (English): | Nature Communications |
| Publisher: | Nature Publishing Group UK |
| Place of publication: | [London] |
| Document Type: | Article |
| Language: | English |
| Year of Completion: | 2018 |
| Date of first Publication: | 2018/01/12 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2018/03/08 |
| Tag: | Homeostasis; Type 2 diabetes |
| Volume: | 9 |
| Issue: | 1, Art. 177 |
| Page Number: | 11 |
| First Page: | 1 |
| Last Page: | 11 |
| Note: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| HeBIS-PPN: | 432787712 |
| Institutes: | Medizin / Medizin |
| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
| Sammlungen: | Universitätspublikationen |
| Licence (German): |  Creative Commons - Namensnennung 4.0 |
