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Dihydromyricetin Attenuates Metabolic Syndrome And Improves Insulin Sensitivity By Upregulating Insulin Receptor Substrate-1 (Y612) Tyrosine Phosphorylation In db/db Mice

Authors He J, Zhang J, Dong L, Dang X, Wang L, Cheng L, Huang Y

Received 6 June 2019

Accepted for publication 1 October 2019

Published 1 November 2019 Volume 2019:12 Pages 2237—2249


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Antonio Brunetti

Jidong He,1 Junpeng Zhang,1 Lijuan Dong,1 Xuefeng Dang,1 Li Wang,2 Long Cheng,3 Yunxiang Huang4

1Department of Gastroenterology, Baoji People’s Hospital, Baoji, Shanxi 721000, People’s Republic of China; 2Department of Diabetic Nephropathy, Baoji Central Hospital, Baoji, Shanxi 721008, People’s Republic of China; 3Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, People’s Republic of China; 4Department of R&D, Asparagus Engineering Research Center of Hebei Province, Qinhuangdao 066008, People’s Republic of China

Correspondence: Li Wang
Baoji Central Hospital, No. 8, Jiangtan Road, Baoji, Shanxi 721008, People’s Republic of China
Long Cheng
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 151, Malianwa North Road Haidian District, Beijing 100094, People’s Republic of China
Tel/Fax +86 10 57833013

Purpose: Dihydromyricetin (DHM), the main bioactive flavonoid in vine tea, exerts multiple health beneficial effects. This work aimed to identify whether a naturally derived flavonoid product, DHM, can significantly attenuate metabolic syndrome and improve insulin sensitivity.
Methods: 10-week-old db/db mice were randomly assigned to receive the antidiabetic agent metformin (Met, 50 mg/kg BW), DHM (1.0 g and 0.5 g/kg BW) or placebo and were simultaneously fed a high-fat diet for 8 weeks. The general status of the animals was observed and recorded daily, body weight and blood glucose levels were measured weekly, during the experimental period. On day 55, the oral glucose tolerance test (OGTT) was performed. After OGTT, all animals were anesthetized and sacrificed by cervical decapitation. Blood samples were collected in tubes to detect plasma insulin and the biochemical parameters of lipid metabolism. Pancreas histological changes and islet fibrosis were demonstrated by H&E staining and Masson staining, respectively. Moreover, the expression of insulin receptor substrate-1 and phosphorylated insulin receptor substrate-1 in the insulin signaling pathway was detected by Western blot assay.
Results: The oral administration of DHM (1.0 g and 0.5 g/kg BW) reduced the fasting blood glucose, serum insulin, and glycated hemoglobin levels and the insulin resistance (HOMA-IR) index. Furthermore, DHM intervention decreased body weight and the serum lipid profile. In addition, DHM treatment also markedly decreased the relative abdominal fat weight. Western blot analysis indicated that DHM upregulated the IRS-1 (Y612) tyrosine phosphorylation, improving insulin resistance. Treatment with dihydromyricetin attenuated the progression of insulin resistance and pancreatic fibrosis in fatty db/db mice.
Conclusion: In summary, we determined the antimetabolic syndrome effect of DHM in db/db obese mice. DHM upregulates the IRS-1 (Y612) tyrosine phosphorylation, improving insulin resistance. Therefore, DHM is a promising therapeutic candidate for the control of metabolic syndrome.

Keywords: dihydromyricetin, metabolic syndrome, hypoglycemic function, insulin resistance, insulin receptor substrate-1

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