Rhein protects pancreatic beta-cells from dynamin-related protein-1-mediated mitochondrial fission and cell apoptosis under hyperglycemia.

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Liu J, Chen Z, Zhang Y, Zhang M, Zhu X, Fan Y, Shi S, Zen K, Liu Z

Rhein protects pancreatic beta-cells from dynamin-related protein-1-mediated mitochondrial fission and cell apoptosis under hyperglycemia.

Diabetes. 2013 Nov;62(11):3927-35. doi: 10.2337/db13-0251. Epub 2013 Aug 6.

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23919963 [ View in PubMed
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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 beta-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 beta-cells indicated that rhein strongly inhibited beta-cell apoptosis. Morphological study showed that rhein was mainly localized at beta-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 beta-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 beta-cells from apoptosis by blocking the hyperglycemia-induced Drp1 expression.

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