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.