Refine
Year of publication
- 2018 (520) (remove)
Document Type
- Article (448)
- Doctoral Thesis (39)
- Contribution to a Periodical (9)
- Part of Periodical (9)
- Preprint (8)
- Book (3)
- Conference Proceeding (3)
- Report (1)
Has Fulltext
- yes (520)
Is part of the Bibliography
- no (520) (remove)
Keywords
- breast cancer (15)
- Mammakarzinom (10)
- Behandlung (8)
- inflammation (7)
- CDK4/6 (6)
- Inflammation (6)
- Metastasen (6)
- Neuroscience (6)
- PD1/PDL1 (6)
- Studien (6)
Institute
- Medizin (520) (remove)
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.