Affiliation:
1. Institute of Basic Medical Sciences, Xi’an Medical University, Xi’an, China
2. School of Biomedical Sciences, University of Queensland, Brisbane, Australia
Abstract
Abstract
The free fatty acid receptor G protein-coupled receptor 120 (GPR120) is expressed in pancreatic islets, but its specific cell distribution and function have not been fully established. In this study, a GPR120-IRES-EGFP knockin (KI) mouse was generated to identify GPR120-expressing cells with enhanced green fluorescence proteins (EGFP). EGFP-positive cells collected from KI mouse islets by flow cytometry had a significantly higher expression of pancreatic polypeptide (PP) evidenced by reverse transcriptase (RT)-quantitative polymerase chain reaction (qPCR). Single-cell RT-PCR and immunocytochemical double staining also demonstrated the coexpression of GPR120 with PP in mouse islets. The GPR120-specific agonist TUG-891 significantly increased plasma PP levels in mice. TUG-891 significantly increased PP levels in islet medium in vitro, which was markedly attenuated by GPR120 small interfering RNA treatment. TUG-891–stimulated PP secretion in islets was fully blocked by pretreatment with YM-254890 (a Gq protein inhibitor), U73122 (a phospholipase C inhibitor), or thapsigargin (an inducer of endoplasmic reticulum Ca2+ depletion), respectively. TUG-891 triggered the increase in intracellular free Ca2+ concentrations ([Ca2+]i) in PP cells, which was also eliminated by YM-254890, U73122, or thapsigargin. GPR120 gene expression was significantly reduced in islets of high-fat diet (HFD)-induced obese mice. TUG-891–stimulated PP secretion was also significantly diminished in vivo and in vitro in HFD-induced obese mice compared with that in normal-chow diet control mice. In summary, this study demonstrated that GPR120 is expressed in mouse islet PP cells and GPR120 activation stimulated PP secretion via the Gq/PLC-Ca2+ signaling pathway in normal-chow diet mice but with diminished effects in HFD-induced obese mice.
Funder
Shaanxi Educational Department
National Natural Science Foundation of China
Science and Technology Resources Project of Shaanxi Province
Cited by
16 articles.
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