Differential role of GPR142 in tryptophan-mediated enhancement of insulin secretion in obese and lean mice
Tryptophan is reportedly the most potent agonist for GPR142. Glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells are enhanced by GPR142-mediated signal. It is not clear, however, if GPR142-mediated signals is solely attributable to GSIS enhancement after tryptophan load in various pathophysiological settings. This study aims to reveal the significance of GPR142 signaling in tryptophan-mediated GSIS enhancement in normal and obese mice. Tryptophan significantly improved glucose tolerance in both lean and DIO mice, but the extent of improvement was bigger in DIO mice with augmented glucose-stimulated insulin secretion (GSIS) enhancement. The same results were obtained in ob/ob mice. GPR142 deletion almost completely blocked tryptophan actions in lean mice, suggesting that GPR142 signaling was solely responsible for the GSIS enhancement. In obese GPR142KO mice, however, a significant amount of tryptophan effects were still observed. Calcium-sensing receptors (CaSR) are also known to recognize tryptophan as ligand. Expression levels of CaSR were significantly elevated in the pancreas of DIO mice, and CaSR antagonist further blocked tryptophan's actions in DIO mice with GPR142 deletion. Although GPR142 signaling had a major role in tryptophan recognition for the enhancement of GSIS in lean mice, other pathways including CaSR signaling also had a significant role in obese mice, which seemed to contribute to the augmented enhancement of GSIS by tryptophan in these animals.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
|---|---|
| Enthalten in: |
PloS one - 13(2018), 6 vom: 11., Seite e0198762 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ueda, Yoko [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.12.2018 Date Revised 10.12.2019 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0198762 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM285343815 |
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| 100 | 1 | |a Ueda, Yoko |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Differential role of GPR142 in tryptophan-mediated enhancement of insulin secretion in obese and lean mice |
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| 500 | |a Date Revised 10.12.2019 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Tryptophan is reportedly the most potent agonist for GPR142. Glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells are enhanced by GPR142-mediated signal. It is not clear, however, if GPR142-mediated signals is solely attributable to GSIS enhancement after tryptophan load in various pathophysiological settings. This study aims to reveal the significance of GPR142 signaling in tryptophan-mediated GSIS enhancement in normal and obese mice. Tryptophan significantly improved glucose tolerance in both lean and DIO mice, but the extent of improvement was bigger in DIO mice with augmented glucose-stimulated insulin secretion (GSIS) enhancement. The same results were obtained in ob/ob mice. GPR142 deletion almost completely blocked tryptophan actions in lean mice, suggesting that GPR142 signaling was solely responsible for the GSIS enhancement. In obese GPR142KO mice, however, a significant amount of tryptophan effects were still observed. Calcium-sensing receptors (CaSR) are also known to recognize tryptophan as ligand. Expression levels of CaSR were significantly elevated in the pancreas of DIO mice, and CaSR antagonist further blocked tryptophan's actions in DIO mice with GPR142 deletion. Although GPR142 signaling had a major role in tryptophan recognition for the enhancement of GSIS in lean mice, other pathways including CaSR signaling also had a significant role in obese mice, which seemed to contribute to the augmented enhancement of GSIS by tryptophan in these animals | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a CASR protein, mouse |2 NLM | |
| 650 | 7 | |a GPR142 protein, mouse |2 NLM | |
| 650 | 7 | |a Receptors, Calcium-Sensing |2 NLM | |
| 650 | 7 | |a Receptors, G-Protein-Coupled |2 NLM | |
| 650 | 7 | |a Glucagon-Like Peptide 1 |2 NLM | |
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| 650 | 7 | |a Tryptophan |2 NLM | |
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| 700 | 1 | |a Iwakura, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Bando, Mika |e verfasserin |4 aut | |
| 700 | 1 | |a Doi, Asako |e verfasserin |4 aut | |
| 700 | 1 | |a Ariyasu, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Inaba, Hidefumi |e verfasserin |4 aut | |
| 700 | 1 | |a Morita, Shuhei |e verfasserin |4 aut | |
| 700 | 1 | |a Akamizu, Takashi |e verfasserin |4 aut | |
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