Epigallocatechin gallate (EGCG) attenuates high glucose-induced insulin signaling blockade in human hepG2 hepatoma cells.
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.
Lin
Chih-Li
CL
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin
Jen-Kun
JK
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D008113:Liver Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D048868:Adaptor Proteins, Signal Transducing; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D002392:Catechin; C045651:epigallocatechin gallate; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D000263:Adenylate Kinase; D005947:Glucose