Insulinotropic and anti-apoptotic effects of nobiletin in INS-1D β-cells
To determine the mechanism underlying anti-diabetic effects of nobiletin, a citrus flavonoid, the effects of nobiletin on insulin secretion and β-cell apoptosis were investigated in the INS-1D β-cell line. Nobiletin increased glucose-induced insulin secretion (GSIS), and inhibited thapsigargin-induc...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-03-01
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| Series: | Journal of Functional Foods |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464616304364 |
| _version_ | 1818723741624958976 |
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| author | Miki Takii Yukiko K. Kaneko Kiriko Akiyama Yuki Aoyagi Yuki Tara Tomohiro Asakawa Makoto Inai Toshiyuki Kan Kiyomitsu Nemoto Tomohisa Ishikawa |
| author_facet | Miki Takii Yukiko K. Kaneko Kiriko Akiyama Yuki Aoyagi Yuki Tara Tomohiro Asakawa Makoto Inai Toshiyuki Kan Kiyomitsu Nemoto Tomohisa Ishikawa |
| author_sort | Miki Takii |
| collection | DOAJ |
| description | To determine the mechanism underlying anti-diabetic effects of nobiletin, a citrus flavonoid, the effects of nobiletin on insulin secretion and β-cell apoptosis were investigated in the INS-1D β-cell line. Nobiletin increased glucose-induced insulin secretion (GSIS), and inhibited thapsigargin-induced apoptosis. Nobiletin also potentiated forskolin-induced cAMP accumulation. The insulinotropic effect was significantly suppressed by the EPAC inhibitor ESI-09, but not by the PKA inhibitor KT-5720. Conversely, the anti-apoptotic effect was inhibited by KT-5720, but not by ESI-09. Nobiletin also inhibited thapsigargin-induced increases in cleaved caspase-3 and JNK phosphorylation, but had no effect on the expression of CHOP. Similar insulinotropic and anti-apoptotic effects were also observed with the extract from Ponkan peels containing nobiletin. These results suggest that nobiletin exerts anti-diabetic effects by increasing GSIS and preventing β-cell apoptosis via cAMP-dependent mechanisms; the former is primarily mediated by EPAC, whereas the latter is due to PKA-induced alleviation of JNK-mediated ER stress. |
| first_indexed | 2024-12-17T21:15:21Z |
| format | Article |
| id | doaj.art-91b3ad4fe08049fdb9a19d4f12a61850 |
| institution | Directory Open Access Journal |
| issn | 1756-4646 |
| language | English |
| last_indexed | 2024-12-17T21:15:21Z |
| publishDate | 2017-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj.art-91b3ad4fe08049fdb9a19d4f12a618502022-12-21T21:32:22ZengElsevierJournal of Functional Foods1756-46462017-03-0130815Insulinotropic and anti-apoptotic effects of nobiletin in INS-1D β-cellsMiki Takii0Yukiko K. Kaneko1Kiriko Akiyama2Yuki Aoyagi3Yuki Tara4Tomohiro Asakawa5Makoto Inai6Toshiyuki Kan7Kiyomitsu Nemoto8Tomohisa Ishikawa9Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, Japan; Corresponding author.Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, JapanSchool of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, JapanSchool of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, JapanSchool of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, JapanDepartment of Molecular Toxicology, Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashishi, Chiba 274-8510, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, JapanTo determine the mechanism underlying anti-diabetic effects of nobiletin, a citrus flavonoid, the effects of nobiletin on insulin secretion and β-cell apoptosis were investigated in the INS-1D β-cell line. Nobiletin increased glucose-induced insulin secretion (GSIS), and inhibited thapsigargin-induced apoptosis. Nobiletin also potentiated forskolin-induced cAMP accumulation. The insulinotropic effect was significantly suppressed by the EPAC inhibitor ESI-09, but not by the PKA inhibitor KT-5720. Conversely, the anti-apoptotic effect was inhibited by KT-5720, but not by ESI-09. Nobiletin also inhibited thapsigargin-induced increases in cleaved caspase-3 and JNK phosphorylation, but had no effect on the expression of CHOP. Similar insulinotropic and anti-apoptotic effects were also observed with the extract from Ponkan peels containing nobiletin. These results suggest that nobiletin exerts anti-diabetic effects by increasing GSIS and preventing β-cell apoptosis via cAMP-dependent mechanisms; the former is primarily mediated by EPAC, whereas the latter is due to PKA-induced alleviation of JNK-mediated ER stress.http://www.sciencedirect.com/science/article/pii/S1756464616304364NobiletinPancreatic β-cellsInsulin secretionβ-Cell apoptosisER stress |
| spellingShingle | Miki Takii Yukiko K. Kaneko Kiriko Akiyama Yuki Aoyagi Yuki Tara Tomohiro Asakawa Makoto Inai Toshiyuki Kan Kiyomitsu Nemoto Tomohisa Ishikawa Insulinotropic and anti-apoptotic effects of nobiletin in INS-1D β-cells Journal of Functional Foods Nobiletin Pancreatic β-cells Insulin secretion β-Cell apoptosis ER stress |
| title | Insulinotropic and anti-apoptotic effects of nobiletin in INS-1D β-cells |
| title_full | Insulinotropic and anti-apoptotic effects of nobiletin in INS-1D β-cells |
| title_fullStr | Insulinotropic and anti-apoptotic effects of nobiletin in INS-1D β-cells |
| title_full_unstemmed | Insulinotropic and anti-apoptotic effects of nobiletin in INS-1D β-cells |
| title_short | Insulinotropic and anti-apoptotic effects of nobiletin in INS-1D β-cells |
| title_sort | insulinotropic and anti apoptotic effects of nobiletin in ins 1d β cells |
| topic | Nobiletin Pancreatic β-cells Insulin secretion β-Cell apoptosis ER stress |
| url | http://www.sciencedirect.com/science/article/pii/S1756464616304364 |
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