title: Rhein protects pancreatic β-cells from dynamin-related protein-1-mediated mitochondrial fission and cell apoptosis under hyperglycemia.
abstract: Rhein, an anthraquinone compound isolated from rhubarb, has been shown to improve glucose metabolism disorders in diabetic mice. The mechanism underlying the protective effect of rhein, however, remains unknown. Here, we demonstrate that rhein can protect the pancreatic β-cells against hyperglycemia-induced cell apoptosis through stabilizing mitochondrial morphology. Oral administration of rhein for 8 or 16 weeks in db/db mice significantly reduced fasting blood glucose (FBG) level and improved glucose tolerance. Cell apoptosis assay using both pancreatic sections and cultured pancreatic β-cells indicated that rhein strongly inhibited β-cell apoptosis. Morphological study showed that rhein was mainly localized at β-cell mitochondria and rhein could preserve mitochondrial ultrastructure by abolishing hyperglycemia-induced mitochondrial fission protein dynamin-related protein 1 (Drp1) expression. Western blot and functional analysis confirmed that rhein protected the pancreatic β-cells against hyperglycemia-induced apoptosis via suppressing mitochondrial Drp1 level. Finally, mechanistic study further suggested that decreased Drp1 level by rhein might be due to its effect on reducing cellular reactive oxygen species. Taken together, our study demonstrates for the first time that rhein can serve as a novel therapeutic agent for hyperglycemia treatment and rhein protects pancreatic β-cells from apoptosis by blocking the hyperglycemia-induced Drp1 expression.
authors.affiliation: Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Zhaohong
authors.initials: Z
authors.lastname: Chen
authors.forename: Yujing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mingchao
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhu
authors.forename: Yun
authors.initials: Y
authors.lastname: Fan
authors.forename: Shaolin
authors.initials: S
authors.lastname: Shi
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D034281:Dynamins / Q000096:biosynthesis; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects; D063154:Mitochondrial Dynamics / Q000187:drug effects*
chemical_list: D000880:Anthraquinones; D001786:Blood Glucose; C486391:Dnm1l protein, mouse; D034281:Dynamins; D005947:Glucose; C020491:rhein
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