Abstract
Objective
To investigate the effect of Dan-gua Fang (丹瓜方) on adenosine 5′-monophosphate (AMP) activated protein kinase (AMPK) α expression in liver and subsequent improvement of glucose and lipid metabolism.
Methods
Forty 13-week-old diabetic Goto-Kakizaki (GK) rats were randomly divided into model, Dan-gua Fang, metformin and simvastatin groups (n=10 for each), and fed high-fat diet ad libitum. Ten Wistar rats were used as normal group and fed normal diet. After 24 weeks, liver expression of AMPKα mRNA was assessed by real-time PCR. AMPKα and phospho-AMPKα protein expression in liver was evaluated by Western blot. Liver histomorphology was carried out after hematoxylin-eosin staining, and blood glucose (BG), glycosylated hemoglobin A1c (HbA1c), food intake and body weight recorded.
Results
Similar AMPKα mRNA levels were found in the Dan-gua Fang group and normal group, slightly higher than the values obtained for the remaining groups (P<0.05). AMPKα protein expression in the Dan-gua Fang group animals was similar to other diabetic rats, whereas phospho-AMPKα (Thr-172) protein levels were markedly higher than in the metformin group and simvastatin group (P<0.05), respectively. However, phosphor-AMPKα/AMPKα ratios were similar in all groups. Dan-gua Fang reduced fasting blood glucose with similar strength to metformin, and was superior in reducing cholesterol, triglycerides, high-density lipoprotein cholesterol as well as improving low-density lipoprotein cholesterol in comparison with simvastatin and metformin. Dan-gua Fang decreases plasma alanine aminotransferase (ALT) significantly.
Conclusion
Dan-gua Fang, while treating phlegm-stasis, could decrease BG and lipid in type 2 diabetic GK rats fed with high-fat diet, and effectively protect liver histomorphology and function. This may be partly explained by increased AMPK expression in liver. Therefore, Dan-gua Fang might be an ideal drug for comprehensive intervention for glucose and lipid metabolism disorders in type 2 diabetes mellitus.
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Supported by the National Natural Science Foundation of China (No. 81173179), the Natural Science Foundation of Fujian Province (No. 2011J01198), the Fujian Medical Innovation Project (No. 2009-CX-19), the Research Foundation of Fujian Health Department (No. Zlcnfm02), the Fujian Provincial Department of Education Category A Projects (No. JA09131), the Fujian Health Department of Traditional Chinese Medicine Research (No. WZY0920), the CHEN Ke-ji Integrative Medicine Development Fund (No. CKJ2008047, CKJ2009004), and the Integrative Medicine of Fujian Key Laboratory of Age-related Diseases Funded Projects (No. 2008J1004-10)
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Lan, Yl., Huang, Sp., Heng, Xp. et al. Dan-gua Fang (丹瓜方) improves glycolipid metabolic disorders by promoting hepatic adenosine 5′-monophosphate activated protein kinase expression in diabetic Goto-Kakizaki rats. Chin. J. Integr. Med. 21, 188–195 (2015). https://doi.org/10.1007/s11655-014-1826-2
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DOI: https://doi.org/10.1007/s11655-014-1826-2