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

Abstract

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

Acknowledgements

The authors gratefully acknowledge the financial assistance of the National Major Drug Discovery Projects (No: 2017ZX 09301025). The authors thank the scientific editors from American Journal Experts for providing professional English language editing of this paper.

Abbreviations

MetS, metabolic syndrome; DHM, dihydromyricetin; db/db, C57BL/KsJ-db/db, T2DM, type 2 diabetes mellitus; Met, metformin; Hb1Ac, glycated hemoglobin A1c; HOMA-IR, homeostatic model assessment of insulin resistance; IRS-1, insulin receptor substrate-1; TCM, traditional Chinese medicine; TC, serum total cholesterol; TG, triglyceride; MDA, malondialdehyde; SOD, superoxide dismutase; IL-1β, interleukin-1β; TNF-α, tumor necrosis factor alpha; HDL-C, high density liptein cholesterol.

Disclosure

Dr Long Cheng reports a grant from National Major Drug Discovery Projects (No: 2017ZX 09301025), during the conduct of the study. The authors report no other conflicts of interest in this work.