Epigallocatechin gallate (EGCG) attenuates high glucose‐induced insulin signaling blockade in human hepG2 hepatoma cells

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.

Preventive Effects of (−)-Epigallocatechin Gallate on Diethylnitrosamine-Induced Liver Tumorigenesis in Obese and Diabetic C57BL/KsJ-db/db Mice

“…In addition, EGCG may also improve metabolic abnormalities by activating AMPK in the liver, which enhances insulin sensitivity and increases fatty acid oxidation but decreases fatty acid synthesis (32). This finding is consistent with recent studies showing that EGCG increases insulin sensitivity and fat oxidation and induces AMPK activity in the liver (36,37). Furthermore, in addition to the improvement of metabolic disorders, activation of AMPK by EGCG also positively contributes to the prevention of hepatotumorigenesis because decreased AMPK activation is implicated in tumor development and therefore may be a tumor suppressor and a promising target for cancer chemoprevention (38).…”

Acetyl‐l‐carnitine inhibits TNF‐α‐induced insulin resistance via AMPK pathway in rat skeletal muscle cells

“…Indeed, our results indicated that ALC did not alone affect Akt phosphorylation significantly, but augment insulin signaling pathway by activating AMPK, which eventually led to Akt activation [24]. Reports concerning interactions between PI-3K/Akt and AMPK are controversial.…”

Effects of (-)-epigallocatechin-3-O-gallate on expression of gluconeogenesisrelated genes in the mouse duodenum

“…Tea is manufactured from the leaves of the plant Camellia sinensis Kuntze (Theaceae) and has been regarded to possess anti-cancer, anti-obesity, antiatherosclerotic, anti-diabetic, anti-bacterial, and antiviral effects (6,12,14,31,33). Many of the beneficial effects of green tea are related to the actions of (−)-epigallocatechin gallate (EGCG), a major component of green tea catechins (14,27,33) (Fig.…”

“…Many of the beneficial effects of green tea are related to the actions of (−)-epigallocatechin gallate (EGCG), a major component of green tea catechins (14,27,33) (Fig. 1).…”