Association of changes in ER stress-mediated signaling pathway with lead-induced insulin resistance and apoptosis in rats and their prevention by A-type dimeric epigallocatechin-3-gallate.
A-type dimeric epigallocatechin-3-gallate (A-type-EGCG-dimer, AEd), a new proanthocyanidins dimer from persimmon fruits, has been shown to have health benefit effects. However, A-type-EGCG-dimer affects gluose metabolism in the liver and the underlying mechanism is not clarified. The present study aims to examine the protective effects of A-type-EGCG-dimer on Pb-induced hepatic insulin resistance, endoplasmic reticulum (ER) stress and apoptosis in rats. Male wistar rats exposed to 0.05% w/v Pb acetate in the drinking water with or without A-type-EGCG-dimer coadministration (200 mg/kg body weight/day, intragastrically) for three months. We found that A-type-EGCG-dimer and pioglitazone supplementation significantly deceased glucose and insulin levels in plasma as compared with the Pb group. A-type-EGCG-dimer markedly prevents Pb-induced oxidative stress, ER stress and apoptosis in livers. A-type-EGCG-dimer and pioglitazone reduced the expression levels of the GRP78, PEPCK, G6Pase, p-PERK, p-IRE1, p-JNK, ATF4, CHOP and increased p-AKT in livers of the Pb group. Moreover, A-type-EGCG-dimer reduced ROS production and restored the activities of SOD and GPx in livers. A-type-EGCG-dimer decreased Bax, cytosolic cytochrome c and cleaved caspase-3 and increased Bcl-2 in livers of Pb-exposed rats. Our results suggest that A-type-EGCG-dimer might be a potential natural candidate for the prevention of hepatic insulin resistance and apoptosis induced by Pb.
['Liu|Chan-Min|CM|', 'Ma|Jie-Qiong|JQ|', 'Sun|Jian-Mei|JM|', 'Feng|Zhao-Jun|ZJ|', 'Cheng|Chao|C|', 'Yang|Wei|W|', 'Jiang|Hong|H|']
D000818:Animals D017209:Apoptosis D001786:Blood Glucose D002392:Catechin D045304:Cytochromes c D019281:Dimerization D029788:Diospyros D000091342:Endoplasmic Reticulum Chaperone BiP D059865:Endoplasmic Reticulum Stress D006801:Humans D007328:Insulin D007333:Insulin Resistance D007854:Lead D008099:Liver D008297:Male D008659:Metabolic Diseases D018384:Oxidative Stress D010936:Plant Extracts D051381:Rats D015398:Signal Transduction
Insulin resistance Apoptosis Liver ER stress A-type EGCG dimer Lead