Dihydromyricetin Ameliorates Inflammation-Induced Insulin Resistance via Phospholipase C-CaMKK-AMPK Signal Pathway.

Abstract

Patients with metabolic syndrome have a higher risk of type II diabetes and cardiovascular disease. The metabolic syndrome has become an urgent public health problem. Insulin resistance is the common pathophysiological basis of metabolic syndrome. The higher incidence of insulin resistance in obese groups is due to increased levels of inflammatory factors during obesity. Therefore, developing a therapeutic strategy for insulin resistance has great significance for the treatment of the metabolic syndrome. Dihydromyricetin, as a bioactive polyphenol, has been used for anti-inflammatory, antitumor, and improving insulin sensitivity. However, the target of DHM and molecular mechanism of DHM for preventing inflammation-induced insulin resistance is still unclear. In this study, we first confirmed the role of dihydromyricetin in inflammation-induced insulin resistance in vivo and in vitro. Then, we demonstrated that dihydromyricetin resisted inflammation-induced insulin resistance by activating Ca2+-CaMKK-AMPK using signal pathway blockers, Ca2+ probes, and immunofluorescence. Finally, we clarified that dihydromyricetin activated Ca2+-CaMKK-AMPK signaling pathway by interacting with the phospholipase C (PLC), its target protein, using drug affinity responsive target stability (DARTS) assay. Our results not only demonstrated that dihydromyricetin resisted inflammation-induced insulin resistance via the PLC-CaMKK-AMPK signal pathway but also discovered that the target protein of dihydromyricetin is the PLC. Our results provided experimental data for the development of dihydromyricetin as a functional food and new therapeutic strategies for treating or preventing PLC.

• Authors: Lianjie Hou, Fangyi Jiang, Bo Huang, Weijie Zheng, Yufei Jiang, Gengyuan Cai, Dewu Liu, Ching Yuan Hu, Chong Wang
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 8542809 ( 2021) ISSN: 1942-0994 [Electronic] United States
• PMID: 34650665 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Lianjie Hou et al.

Chemical References

• Flavonols
• Calcium-Calmodulin-Dependent Protein Kinase Kinase
• AMP-Activated Protein Kinases
• dihydromyricetin

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Calcium-Calmodulin-Dependent Protein Kinase Kinase (metabolism)
• Diabetes Mellitus, Type 2 (metabolism)
• Flavonols (pharmacology)
• Inflammation (complications)
• Insulin Resistance (physiology)
• Male
• Mice, Inbred C57BL
• Signal Transduction (drug effects)