Lysophosphatidylinositol-induced activation of the cation channel TRPV2 triggers glucagon-like peptide-1 secretion in enteroendocrine L cells.
In: Journal of Biological Chemistry, Jg. 292 (2017-06-30), Heft 26, S. 10855-10864
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Zugriff:
The lysophosphatidylinositol (LPI) has crucial roles in multiple physiological processes, including insulin exocytosis from pancreatic islets. However, the role of LPI in secretion of glucagon- like peptide-1 (GLP-1), a hormone that enhances glucoseinduced insulin secretion, is unclear. Here, we used the murine enteroendocrine L cell line GLUTag and primary murine small intestinal cells to elucidate the mechanism of LPI-induced GLP-1 secretion. Exogenous LPI addition increased intracellular Ca2+ concentrations ([Ca2+]i) in GLUTag cells and induced GLP-1 secretion from both GLUTag and acutely prepared primary intestinal cells. The [Ca2+]iincrease was suppressed by an antagonist for G protein-coupled receptor 55 (GPR55) and by silencing of GPR55 expression, indicating involvement of Gq and G12/13 signaling pathways in the LPI-induced increased [Ca2+]ilevels and GLP-1 secretion. However, GPR55 agonists did not mimic many of the effects of LPI. We also found that phospholipase C inhibitor and Rho-associated kinase inhibitor suppressed the [Ca2+]iincrease and that LPI increased the number of focal adhesions, indicating actin reorganization. Of note, blockage or silencing of transient receptor potential cation channel subfamily V member 2 (TRPV2) channels suppressed both the LPI-induced [Ca2+]iincrease and GLP-1 secretion. Furthermore, LPI accelerated TRPV2 translocation to the plasma membrane, which was significantly suppressed by a GPR55 antagonist. These findings suggest that TRPV2 activation via actin reorganization induced by Gq and G12/13 signaling is involved in LPI-stimulated GLP-1 secretion in enteroendocrine L cells. Because GPR55 agonists largely failed to mimic the effects of LPI, its actions on L cells are at least partially independent of GPR55 activation. [ABSTRACT FROM AUTHOR]
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Lysophosphatidylinositol-induced activation of the cation channel TRPV2 triggers glucagon-like peptide-1 secretion in enteroendocrine L cells.
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Autor/in / Beteiligte Person: | Harada, Kazuki ; Kitaguchi, Tetsuya ; Kamiya, Taichi ; Kyaw Htet Aung ; Nakamura, Kazuaki ; Ohta, Kunihiro ; Tsuboi, Takashi |
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Zeitschrift: | Journal of Biological Chemistry, Jg. 292 (2017-06-30), Heft 26, S. 10855-10864 |
Veröffentlichung: | 2017 |
Medientyp: | academicJournal |
ISSN: | 0021-9258 (print) |
DOI: | 10.1074/jbc.M117.788653 |
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