Nobiletin ameliorates glucose tolerance by protecting against β-cell loss in type-2 diabetic db/db mice
Background: Nobiletin, a polymethoxy flavone contained in the peel of Citrus reticulata, has been known to have health benefits especially those related to improvement of type 2 diabetes. Our previous in vitro study demonstrated the insulinotropic and anti-apoptotic effects of nobiletin in pancreati...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Phytomedicine Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667031322001464 |
| _version_ | 1828097339824275456 |
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| author | Yukiko K. Kaneko Yuki Tara Stella Amarachi Ihim Moe Yamamoto Megumi Kaji Tomohisa Ishikawa |
| author_facet | Yukiko K. Kaneko Yuki Tara Stella Amarachi Ihim Moe Yamamoto Megumi Kaji Tomohisa Ishikawa |
| author_sort | Yukiko K. Kaneko |
| collection | DOAJ |
| description | Background: Nobiletin, a polymethoxy flavone contained in the peel of Citrus reticulata, has been known to have health benefits especially those related to improvement of type 2 diabetes. Our previous in vitro study demonstrated the insulinotropic and anti-apoptotic effects of nobiletin in pancreatic β-cells. These effects of nobiletin are postulated to be responsible for its anti-diabetic activity. Purpose: We evaluated the anti-diabetic effects of nobiletin on pancreatic β-cells of type 2 diabetic db/db mice. Methods: Nobiletin was filled into an osmotic pump and implanted subcutaneously in the back of db/db mice for 2 weeks with continuous administration. The mice were then used for the experiments to elucidate the in vivo effects of nobiletin on glucose intolerance. Results: The continuous subcutaneous administration of nobiletin using osmotic pumps significantly reduced blood glucose levels in non-fasting state and during an oral glucose tolerance test. The nobiletin administration also ameliorated insulin sensitivity determined by insulin tolerance test, which was likely due to a reduction of white adipose tissue weight. In addition, β-cell mass was significantly larger in nobiletin-administered db/db mice compared to vehicle-administered db/db mice. These results suggest that continuous administration of nobiletin ameliorates glucose tolerance in type 2 diabetes, which is mediated by improving not only insulin resistance but also insulin secretion, the latter being due to protection against β-cell loss in diabetes. Conclusion: Nobiletin would have a valuable effect on the prevention of type 2 diabetes. |
| first_indexed | 2024-04-11T07:44:48Z |
| format | Article |
| id | doaj.art-1f45d57433f343509be7c2f6f45b2511 |
| institution | Directory Open Access Journal |
| issn | 2667-0313 |
| language | English |
| last_indexed | 2024-04-11T07:44:48Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Phytomedicine Plus |
| spelling | doaj.art-1f45d57433f343509be7c2f6f45b25112022-12-22T04:36:20ZengElsevierPhytomedicine Plus2667-03132022-11-0124100367Nobiletin ameliorates glucose tolerance by protecting against β-cell loss in type-2 diabetic db/db miceYukiko K. Kaneko0Yuki Tara1Stella Amarachi Ihim2Moe Yamamoto3Megumi Kaji4Tomohisa Ishikawa5Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan; Corresponding author.Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, JapanBackground: Nobiletin, a polymethoxy flavone contained in the peel of Citrus reticulata, has been known to have health benefits especially those related to improvement of type 2 diabetes. Our previous in vitro study demonstrated the insulinotropic and anti-apoptotic effects of nobiletin in pancreatic β-cells. These effects of nobiletin are postulated to be responsible for its anti-diabetic activity. Purpose: We evaluated the anti-diabetic effects of nobiletin on pancreatic β-cells of type 2 diabetic db/db mice. Methods: Nobiletin was filled into an osmotic pump and implanted subcutaneously in the back of db/db mice for 2 weeks with continuous administration. The mice were then used for the experiments to elucidate the in vivo effects of nobiletin on glucose intolerance. Results: The continuous subcutaneous administration of nobiletin using osmotic pumps significantly reduced blood glucose levels in non-fasting state and during an oral glucose tolerance test. The nobiletin administration also ameliorated insulin sensitivity determined by insulin tolerance test, which was likely due to a reduction of white adipose tissue weight. In addition, β-cell mass was significantly larger in nobiletin-administered db/db mice compared to vehicle-administered db/db mice. These results suggest that continuous administration of nobiletin ameliorates glucose tolerance in type 2 diabetes, which is mediated by improving not only insulin resistance but also insulin secretion, the latter being due to protection against β-cell loss in diabetes. Conclusion: Nobiletin would have a valuable effect on the prevention of type 2 diabetes.http://www.sciencedirect.com/science/article/pii/S2667031322001464Pancreatic β-cellsβ-cell massInsulin secretionInsulin sensitivityNobiletin |
| spellingShingle | Yukiko K. Kaneko Yuki Tara Stella Amarachi Ihim Moe Yamamoto Megumi Kaji Tomohisa Ishikawa Nobiletin ameliorates glucose tolerance by protecting against β-cell loss in type-2 diabetic db/db mice Phytomedicine Plus Pancreatic β-cells β-cell mass Insulin secretion Insulin sensitivity Nobiletin |
| title | Nobiletin ameliorates glucose tolerance by protecting against β-cell loss in type-2 diabetic db/db mice |
| title_full | Nobiletin ameliorates glucose tolerance by protecting against β-cell loss in type-2 diabetic db/db mice |
| title_fullStr | Nobiletin ameliorates glucose tolerance by protecting against β-cell loss in type-2 diabetic db/db mice |
| title_full_unstemmed | Nobiletin ameliorates glucose tolerance by protecting against β-cell loss in type-2 diabetic db/db mice |
| title_short | Nobiletin ameliorates glucose tolerance by protecting against β-cell loss in type-2 diabetic db/db mice |
| title_sort | nobiletin ameliorates glucose tolerance by protecting against β cell loss in type 2 diabetic db db mice |
| topic | Pancreatic β-cells β-cell mass Insulin secretion Insulin sensitivity Nobiletin |
| url | http://www.sciencedirect.com/science/article/pii/S2667031322001464 |
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