Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 Pathway
Chronic hyperglycemia increases apoptosis and reduces glucose-stimulated insulin secretion. Although protective agents have been searched extensively, none has been found so far. Here we tested FLZ, a synthetic derivative of squamosamide from a Chinese herb, as a potential candidate for antiglucotox...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/803986 |
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| _version_ | 1832558465561657344 |
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| author | Xiangchen Kong Longmei Zhang Xianxin Hua Xiaosong Ma |
| author_facet | Xiangchen Kong Longmei Zhang Xianxin Hua Xiaosong Ma |
| author_sort | Xiangchen Kong |
| collection | DOAJ |
| description | Chronic hyperglycemia increases apoptosis and reduces glucose-stimulated insulin secretion. Although protective agents have been searched extensively, none has been found so far. Here we tested FLZ, a synthetic derivative of squamosamide from a Chinese herb, as a potential candidate for antiglucotoxicity in INS-1E cells and mouse islets. Chronic culture of β-cells in 30 mM glucose caused progressive reduction of cell viability, accompanied with increased apoptosis and reduced insulin secretion. These effects on apoptosis and insulin were reversed by FLZ in a dose-dependent manner. FLZ treatment also increased forkhead box O1 protein phosphorylation and reduced its nuclear location. On the contrary, FLZ increased pancreatic and duodenal homeobox-1 expression and its nuclear localization, an effect mediated by increased p-Akt. Consistently, Akt selective inhibitor MK-2206 completely abolished antiglucotoxicity effect of FLZ. Furthermore, FLZ treatment increased cytosolic ATP/ADP ratio. Taken together, our results suggest that FLZ could be a potential therapeutic agent to treat the hyperglycemia-induced β-cell failure. |
| format | Article |
| id | doaj-art-8c228e28c4fa43f3b924a321378c6cb1 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-8c228e28c4fa43f3b924a321378c6cb12025-02-03T01:32:18ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/803986803986Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 PathwayXiangchen Kong0Longmei Zhang1Xianxin Hua2Xiaosong Ma3Diabetes Center, Shenzhen University, Shenzhen 518060, ChinaDiabetes Center, Shenzhen University, Shenzhen 518060, ChinaDiabetes Center, Shenzhen University, Shenzhen 518060, ChinaDiabetes Center, Shenzhen University, Shenzhen 518060, ChinaChronic hyperglycemia increases apoptosis and reduces glucose-stimulated insulin secretion. Although protective agents have been searched extensively, none has been found so far. Here we tested FLZ, a synthetic derivative of squamosamide from a Chinese herb, as a potential candidate for antiglucotoxicity in INS-1E cells and mouse islets. Chronic culture of β-cells in 30 mM glucose caused progressive reduction of cell viability, accompanied with increased apoptosis and reduced insulin secretion. These effects on apoptosis and insulin were reversed by FLZ in a dose-dependent manner. FLZ treatment also increased forkhead box O1 protein phosphorylation and reduced its nuclear location. On the contrary, FLZ increased pancreatic and duodenal homeobox-1 expression and its nuclear localization, an effect mediated by increased p-Akt. Consistently, Akt selective inhibitor MK-2206 completely abolished antiglucotoxicity effect of FLZ. Furthermore, FLZ treatment increased cytosolic ATP/ADP ratio. Taken together, our results suggest that FLZ could be a potential therapeutic agent to treat the hyperglycemia-induced β-cell failure.http://dx.doi.org/10.1155/2015/803986 |
| spellingShingle | Xiangchen Kong Longmei Zhang Xianxin Hua Xiaosong Ma Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 Pathway Journal of Diabetes Research |
| title | Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 Pathway |
| title_full | Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 Pathway |
| title_fullStr | Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 Pathway |
| title_full_unstemmed | Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 Pathway |
| title_short | Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 Pathway |
| title_sort | squamosamide derivative flz protects pancreatic β cells from glucotoxicity by stimulating akt foxo1 pathway |
| url | http://dx.doi.org/10.1155/2015/803986 |
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