Glutamine-induced signaling pathways via amino acid receptors in enteroendocrine L cell lines
| Autor: | Tadafumi Kato, Takumi Nakamura, Kunihiro Ohta, Tetsuya Kitaguchi, Kazuki Harada, Taichi Kamiya, Jim Küppers, Kazuo Nakajima, Mai Takizawa, Michael Gütschow, Takashi Tsuboi |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell signaling Enteroendocrine Cells Glutamine 030209 endocrinology & metabolism Enteroendocrine cell Receptors G-Protein-Coupled 03 medical and health sciences Mice 0302 clinical medicine Endocrinology L Cells Glucagon-Like Peptide 1 Extracellular Cyclic AMP Glucose homeostasis Animals Receptors Amino Acid Secretion Receptor Molecular Biology Cells Cultured G protein-coupled receptor Secretory Pathway Chemistry Cell biology 030104 developmental biology Signal transduction Signal Transduction |
| Zdroj: | Journal of molecular endocrinology. 64(3) |
| ISSN: | 1479-6813 |
| Popis: | Glucagon-like peptide-1 (GLP-1), secreted by gastrointestinal enteroendocrine L cells, induces insulin secretion and is important for glucose homeostasis. GLP-1 secretion is induced by various luminal nutrients, including amino acids. Intracellular Ca2+ and cAMP dynamics play an important role in GLP-1 secretion regulation; however, several aspects of the underlying mechanism of amino acid-induced GLP-1 secretion are not well characterized. We investigated the mechanisms underlying the L-glutamine-induced increase in Ca2+ and cAMP intracellular concentrations ([Ca2+]i and [cAMP]i, respectively) in murine enteroendocrine L cell line GLUTag cells. Application of L-glutamine to cells under low extracellular [Na+] conditions, which inhibited the function of the sodium-coupled L-glutamine transporter, did not induce an increase in [Ca2+]i. Application of G protein-coupled receptor family C group 6 member A and calcium-sensing receptor antagonist showed little effect on [Ca2+]i and [cAMP]i; however, taste receptor type 1 member 3 (TAS1R3) antagonist suppressed the increase in [cAMP]i. To elucidate the function of TAS1R3, which forms a heterodimeric umami receptor with taste receptor type 1 member 1 (TAS1R1), we generated TAS1R1 and TAS1R3 mutant GLUTag cells using the CRISPR/Cas9 system. TAS1R1 mutant GLUTag cells exhibited L-glutamine-induced increase in [cAMP]i, whereas some TAS1R3 mutant GLUTag cells did not exhibit L-glutamine-induced increase in [cAMP]i and GLP-1 secretion. These findings suggest that TAS1R3 is important for L-glutamine-induced increase in [cAMP]i and GLP-1 secretion. Thus, TAS1R3 may be coupled with Gs and related to cAMP regulation. |
| Databáze: | OpenAIRE |
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