Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Diabetologia. 2014 Jun;57(6):1182-91. doi: 10.1007/s00125-014-3213-0. Epub 2014 Mar 25.

GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans.

Author information

1
Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, RILD Building, Barrack Road, Exeter, EX2 5DW, UK.

Abstract

AIMS/HYPOTHESIS:

The NEFA-responsive G-protein coupled receptor 120 (GPR120) has been implicated in the regulation of inflammation, in the control of incretin secretion and as a predisposing factor influencing the development of type 2 diabetes by regulation of islet cell apoptosis. However, there is still considerable controversy about the tissue distribution of GPR120 and, in particular, it remains unclear which islet cell types express this molecule. In the present study, we have addressed this issue by constructing a Gpr120-knockout/β-galactosidase (LacZ) knock-in (KO/KI) mouse to examine the distribution and functional role of GPR120 in the endocrine pancreas.

METHODS:

A KO/KI mouse was generated in which exon 1 of the Gpr120 gene (also known as Ffar4) was replaced in frame by LacZ, thereby allowing for regulated expression of β-galactosidase under the control of the endogenous GPR120 promoter. The distribution of GPR120 was inferred from expression studies detecting β-galactosidase activity and protein production. Islet hormone secretion was measured from isolated mouse islets treated with selective GPR120 agonists.

RESULTS:

β-galactosidase activity was detected as a surrogate for GPR120 expression exclusively in a small population of islet endocrine cells located peripherally within the islet mantle. Immunofluorescence analysis revealed co-localisation with somatostatin suggesting that GPR120 is preferentially produced in islet delta cells. In confirmation of this, glucose-induced somatostatin secretion was inhibited by a range of selective GPR120 agonists. This response was lost in GPR120-knockout mice.

CONCLUSIONS/INTERPRETATION:

The results imply that GPR120 is selectively present within the delta cells of murine islets and that it regulates somatostatin secretion.

PMID:
24663807
PMCID:
PMC4018485
DOI:
10.1007/s00125-014-3213-0
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center