Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 Pathway
Joint Authors
Kong, Xiangchen
Zhang, Longmei
Ma, Xiaosong
Hua, Xianxin
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-06-17
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Kong, Xiangchen& Zhang, Longmei& Hua, Xianxin& Ma, Xiaosong. 2015. Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 Pathway. Journal of Diabetes Research،Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1068005
Modern Language Association (MLA)
Kong, Xiangchen…[et al.]. Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 Pathway. Journal of Diabetes Research No. 2015 (2015), pp.1-9.
https://search.emarefa.net/detail/BIM-1068005
American Medical Association (AMA)
Kong, Xiangchen& Zhang, Longmei& Hua, Xianxin& Ma, Xiaosong. Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 Pathway. Journal of Diabetes Research. 2015. Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1068005
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1068005