Epigallocatechin-3-gallate ameliorates insulin resistance in hepatocytes

Abstract

Hyperglycemia is a typical pathogenic factor in a series of complications among patients with type II diabetes. Epigallocatechin-3-gallate (EGCG) is the major polyphenol extracted from green tea and is reported to be an antioxidant. The aim of the present study was to examine the effect of EGCG on insulin resistance in human HepG2 cells pretreated with high concentrations of glucose. The protein kinase B (AKT)/glycogen synthase kinase (GSK) pathways were analyzed using western blot analysis in HepG2 cells and primary mouse hepatocytes treated with high glucose and/or EGCG. Cellular glycogen content was determined using a glycogen assay kit. Reactive oxygen species (ROS) production was determined using dihydroethidium staining and flow cytometry. c‑JUN N‑terminal kinase (JNK)/insulin receptor substrate 1 (IRS1)/AKT/GSK signaling was explored using western blot analysis in HepG2 cells treated with high glucose and/or EGCG or N-acetyl-cysteine. High glucose significantly decreased the levels of phosphorylated AKT and GSK in HepG2 cells and mouse primary hepatocytes. Pretreatment with EGCG significantly restored the activation of AKT and GSK in HepG2 cells and primary hepatocytes exposed to high glucose. In HepG2 cells and primary hepatocytes, glycogen synthesis was improved by EGCG treatment in a dose‑dependent manner. High glucose significantly stimulated the production of ROS while EGCG protected high glucose‑induced ROS production. ROS is known to serve a major role in high glucose induced‑insulin resistance by increasing JNK and IRS1 serine phosphorylation. In the present study, EGCG was observed to enhance the insulin‑signaling pathway. EGCG ameliorated high glucose‑induced insulin resistance in the hepatocytes by potentially decreasing ROS‑induced JNK/IRS1/AKT/GSK signaling.

Fu Brick Tea Alleviates Chronic Kidney Disease of Rats with High Fat Diet Consumption through Attenuating Insulin Resistance in Skeletal Muscle

“…EGCG and other catechins can improve insulin sensitivity by reversing insulin signal defects in vivo. 35,36 Here, FTE richness in EGCG was able to restore insulin pathways against HFD damage in rats. These beneficial effects could promote glucose absorption and improve the effect of glucose tolerance on HFD-induced insulin resistance.…”

Quercetin and Green Tea Extract Supplementation Downregulates Genes Related to Tissue Inflammatory Responses to a 12-Week High Fat-Diet in Mice

“…EGCG, a catechin, is the most abundant flavonoid found in green tea [ 6 ] and has been reported to have anti-obesity, anti-diabetic, and anti-inflammatory properties [ 2 , 3 , 37 ]. Notably, in vitro studies indicate that EGCG suppressed insulin resistance [ 38 , 39 ] and promoted glucose uptake via enhanced GLUT4 translocation [ 39 , 40 ] in skeletal muscle cells, attenuated β-cell release of insulin from mouse and human islet cells [ 39 ], and improved insulin sensitivity in human hepatocytes (HepG2 cells) [ 41 ]. Furthermore, EGCG was associated with decreased glucose uptake [ 42 ], lipid accumulation [ 43 , 44 , 45 ], adipogenesis [ 46 ], and adipocyte differentiation [ 44 ] in 3T3-L1 adipocytes, and reduced inflammation by reactive oxygen species generation in macrophages [ 47 ].…”

Modulation of Glucose Metabolism by Leaf Tea Constituents: A Systematic Review of Recent Clinical and Pre-clinical Findings

“…Against this background, several studies have demonstrated that tea constituents could improve glucose metabolism in animal and cell culture models by enhancing insulin signaling through the IRS/PI3K/AKT pathway in the liver and muscle, and by regulating the content and activity of glucose transporters in these tissues (Table ). − …”