Premium
Epigallocatechin gallate (EGCG) attenuates high glucose‐induced insulin signaling blockade in human hepG2 hepatoma cells
Author(s) -
Lin ChihLi,
Lin JenKun
Publication year - 2008
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200700437
Subject(s) - insulin resistance , insulin receptor , medicine , insulin receptor substrate , ampk , insulin , endocrinology , protein kinase b , phosphorylation , glycogen synthase , glucose uptake , irs1 , chemistry , signal transduction , protein kinase a , biology , biochemistry
Abstract Insulin resistance is the primary characteristic of type 2 diabetes which as a result of insulin signaling defects. It has been suggested that the tea polyphenol (–)‐epigallocatechin‐3‐gallate (EGCG) displays some antidiabetic effects, but the mechanism for EGCG insulin‐enhancing effects is incompletely understood. In the present study, the investigations of EGCG on insulin signaling are performed in insulin‐responsive human HepG2 cells cotreated with high glucose. We found that the high glucose condition causes significant increasing Ser307 phosphorylation of insulin receptor substrate‐1 (IRS‐1), leading to reduce insulin‐stimulated phosphorylation of Akt. As the results, the insulin metabolic effects of glycogen synthesis and glucose uptake are inhibited by high glucose. However, the treatment of EGCG improves insulin‐stimulated downsignaling by reducing IRS‐1 Ser307 phosphorylation. Furthermore, we also demonstrated these EGCG effects are essential depends on the 5′‐AMP‐activated protein kinase (AMPK) activation. Together, our data suggest a putative link between high glucose and insulin resistance in HepG2 cells, and the EGCG treatment attenuates insulin signaling blockade by reducing IRS‐1 Ser307 phosphorylation through the AMPK activation pathway.