Citrus flavone tangeretin is a potential insulin sensitizer targeting hepatocytes through suppressing MEK-ERK1/2 pathway.

Abstract

BACKGROUND:

Tangeretin, a flavonoid derived from citrus peel, showed anti-diabetic effects. However, the role of tangeretin on liver, the organ that act as target of insulin and play the central role in maintaining the blood glucose level control, is still largely unknown. The current study was designed to assess the effect of tangeretin on liver insulin sensitivity in vitro and in vivo.

METHODS:

Primary hepatocytes and mice were treated with different dose of tangeretin, parameters of insulin sensitivity, such as blood glucose levels, serum insulin levels, glucose tolerate test (GTT), insulin tolerate test (ITT), insulin stimulated IR-AKT pathway were analyzed.

RESULTS:

Primary hepatocytes treated with 10/20 μM tangeretin showed up-regulated insulin signaling pathway as well as the glycogen content, while the glucose output were reduced. Intragastric administration of tangeretin (25/50 mg/kg) also ameliorated the liver insulin sensitivity and improved the glucose homeostasis, both in wild type C57 mice and in db/db mice, a diabetic model. Tangeretin treatment dose-dependently suppressed the MEK-ERK1/2 pathway, while forced activation of p-ERK1/2 reversed the insulin sensitized effect of tangeretin.

CONCLUSION:

These results indicated that tangeretin enhanced the liver insulin sensitivity in vitro and in vivo, through suppressing the MEK-ERK1/2 pathway.

• Authors: Jianjin Guo, Jinfeng Chen, Wei Ren, Yikun Zhu, Qian Zhao, Kaini Zhang, Dongming Su, Chen Qiu, Wei Zhang, Kai Li
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 529 Issue 2 Pg. 277-282 (08 20 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 32703423 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Flavones
• Insulin
• tangeretin

Topics

• Animals
• Cells, Cultured
• Citrus (chemistry)
• Flavones (chemistry, pharmacology)
• Hepatocytes (drug effects, metabolism)
• Insulin (metabolism)
• Insulin Resistance
• MAP Kinase Signaling System (drug effects)
• Male
• Mice, Inbred C57BL