Free fatty acid receptor 1 stimulates cAMP production and gut hormone secretion through Gq-mediated activation of adenylate cyclase 2.

ABSTRACT:

Objective

Free fatty acid receptor 1 (FFAR1) is highly expressed in enteroendocrine cells of the small intestine and pancreatic beta cells, where FFAR1 agonists function as GLP-1 and insulin secretagogues, respectively. Most efficacious are so-called second-generation synthetic agonists such as AM5262, which, in contrast to endogenous long-chain fatty acids are able to signal through both IP₃/Ca²⁺ and cAMP pathways. Whereas IP₃ signaling is to be expected for the mainly Gq-coupled FFAR1, the mechanism behind FFAR1-induced cAMP accumulation remains unclear, although originally proposed to be Gs mediated.

Methods and results

When stimulated with AM5262, we observe that FFAR1 can activate the majority of the Gα proteins, except - surprisingly -

SUBMITTER: Petersen JE 

PROVIDER: S-EPMC10394103 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature