Emodin regulates glucose utilization by activating AMP-activated protein kinase
SCIE
SCOPUS
- Title
- Emodin regulates glucose utilization by activating AMP-activated protein kinase
- Authors
- Song, P; Kim, JH; Ghim, J; Yoon, JH; Lee, A; Kwon, Y; Hyun, H; Moon, HY; Choi, HS; Berggren, PO; Suh, PG; Ryu, SH
- Date Issued
- 2013-02-22
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Abstract
- AMP-activated protein kinase has been described as a key signaling protein that can regulate energy homeostasis. Here, we aimed to characterize novel AMP-activated kinase (AMPK)-activating compounds that have a much lower effective concentration than metformin. As a result, emodin, a natural anthraquinone derivative, was shown to stimulate AMPK activity in skeletal muscle and liver cells. Emodin enhanced GLUT4 translocation and [C-14]glucose uptake into the myotube in an AMPK-dependent manner. Also, emodin inhibited glucose production by suppressing the expression of key gluconeogenic genes, such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, in hepatocytes. Furthermore, we found that emodin can activate AMPK by inhibiting mitochondrial respiratory complex I activity, leading to increased reactive oxygen species and Ca2+/calmodulin-dependent protein kinase kinase activity. Finally, we confirmed that a single dose administration of emodin significantly decreased the fasting plasma glucose levels and improved glucose tolerance in C57Bl/6J mice. Increased insulin sensitivity was also confirmed after daily injection of emodin for 8 days using an insulin tolerance test and insulin-stimulated PI3K phosphorylation in wild type and high fat diet-induced diabetic mouse models. Our study suggests that emodin regulates glucose homeostasis in vivo by AMPK activation and that this may represent a novel therapeutic principle in the treatment of type 2 diabetic models.
- Keywords
- 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; DEPENDENT DIABETES-MELLITUS; RAT SKELETAL-MUSCLE; COMPLEX-I; SIGNALING PATHWAY; ADIPOSE-TISSUE; INSULIN; METFORMIN; CELLS; TRANSPORT
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/16191
- DOI
- 10.1074/JBC.M112.441477
- ISSN
- 0021-9258
- Article Type
- Article
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 288, no. 8, page. 5732 - 5742, 2013-02-22
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