Journal
LIFE SCIENCES
Volume 149, Issue -, Pages 58-64Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2016.02.044
Keywords
Gossypol; Diabetes type 2; High fat diet; Liver fibrosis; 11 beta-hydroxysteroid dehydrogenase
Funding
- Health Bureau of Zhejiang Province [WRJ2011-2-012, 11-CX29, 2013ZDA017]
- Zhejiang Science Technology [2007C34003]
- Wenzhou Bureau of Science and Technology [Y20120010]
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11 beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD1) inhibitors have been shown to treat type 2 diabetes (T2D). Since gossypol is an 11 beta -HSD1 inhibitor, the objective of the present study was to treat T2D and T2D-related liver fibrosis in rat model using low-dose gossypol. T2D was induced by feeding with high fat diet plus injection of streptozocin (30 mg/kg). Diabetic rats were treated with either vehicle control or racemic gossypol with a dose of 15 mg/kg/day for 4 weeks followed by 15 mg/kg/week for additional 8 weeks. Blood glucose, cholesterol, LDL, and triglycerides were measured. Messenger mRNA levels of glucocorticoid receptor (Nr3c1), phosphoenolpyruvate carboxykinase (Pck1), glucose-6-phosphatase (G6pc), collagen I (Col1a1), collagen III (Col3a1), fibronectin (Fn1), tissue inhibitor of metalloproteinase 1 (Timp1), and 2 (Timp2) were measured. T2D rats had higher serum glucose, cholesterol, LDL, and triglyceride levels compared to control. Liver Nr3c1, Col1a1, Col3a1, Fn1, Timp1, and Timp2 were increased in T2D rats. T2D liver showed significant fibrosis with the increases of a-smooth muscle actin and fibronectin. After gossypol treatment, serum glucose level was lowered by 64%. Liver fibrosis was significantly ameliorated. Nr3c1, Col1a1, Col3a1, Fn1, Timp1, Timp2, Pck1 as well as G6pc levels were significantly reduced. In conclusion, low dose gossypol is effective for the treatment of T2D and T2D-related fibrosis. (C) 2016 Elsevier Inc. All rights reserved.
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