GPR142 Agonists Stimulate Glucose-Dependent Insulin Secretion via Gq-Dependent Signaling.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27104960.
- Also identified by DOI 10.1371/journal.pone.0154452 and PMC identifier 4841597.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
GPR142 is an islet-enriched G protein-coupled receptor that has been investigated as a novel therapeutic target for the treatment of type 2 diabetes by virtue of its insulin secretagogue activity. However, the signaling pathways downstream of GPR142 and whether its stimulation of insulin release is glucose-dependent remain poorly characterized. In this study, we show that both native and synthetic GPR142 agonists can activate Gq as well as Gi signaling when GPR142 is recombinantly expressed in HEK293 cells. However, in primary pancreatic islets, a native cellular system, the insulin secretagogue activity of GPR142 agonists only requires Gq activation. In addition, our results show that stimulation of insulin secretion by GPR142 in pancreatic islets is strictly glucose-dependent.
Medical subject headings
- Aminopyridines
- Glucose
- Insulin
- Protein Subunits
- Pyrazoles
- Receptors, G-Protein-Coupled
- Tryptophan