| First Author | Tunaru S | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 177 |
| PubMed ID | 29330456 | Mgi Jnum | J:260097 |
| Mgi Id | MGI:6114911 | Doi | 10.1038/s41467-017-02539-4 |
| Citation | Tunaru S, et al. (2018) 20-HETE promotes glucose-stimulated insulin secretion in an autocrine manner through FFAR1. Nat Commun 9(1):177 |
| abstractText | The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic beta-cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote glucose-stimulated insulin secretion (GSIS). However, the physiological role of FFAR1 in beta-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 alpha-linolenic acid. Murine and human beta-cells produce 20-HETE, and the omega-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. |
