PGBR extract ameliorates TNF-α induced insulin resistance in hepatocytes

Pre-germinated brown rice (PGBR) could ameliorate metabolic syndrome, however, not much research estimates the effect of PGBR extract on insulin resistance. The aim of this study is to examine the effects of PGBR extract in TNF-alpha induced insulin resistance. HepG2 cells, hepatocytes, were cultured in DMEM medium and added with 5 mu M insulin or with insulin and 30 ng/ml TNF-alpha or with insulin, TNF-alpha and PGBR extract (50, 100, 300 mu g/ml). The glucose levels of the medium were decreased by insulin, demonstrating insulin promoted glucose uptake into cell. However, TNF-alpha inhibited glucose uptake into cells treated with insulin. Moreover, insulin increased the protein expressions of AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase-alpha (PI3K-alpha), serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB), glucose transporter-2 (GLUT-2), glucokinase (GCK), peroxisome proliferator activated receptor-alpha (PPAR-alpha) and PPAR-gamma. TNF-alpha activated p65 and MAPKs (JNK1/2 and ERK1/2) which worsened the expressions of AMPK, IRS-1, PI3K-alpha, Akt/PKB, GLUT-2, GCK, glycogen synthase kinase-3 (GSK-3), PPAR-alpha and PPAR-gamma. Once this relationship was established, we added PGBR extract to cell with insulin and TNF-alpha. We found glucose levels of medium were lowered and that the protein expressions of AMPK, IRS-1, PI3K-alpha, Akt/PKB, GLUT-2, GCK, GSK-3, PPAR-alpha, PPAR-gamma and p65, JNK1/2 were also recovered. In conclusion, this study found that TNF-alpha inhibited insulin stimulated glucose uptake and aggravated related proteins expressions, suggesting that it might cause insulin resistance. PGBR extract was found to ameliorate this TNF-alpha induced insulin resistance, suggesting that it might be used in the future to help control insulin resistance. Copyright (C) 2017, Kaohsiung Medical University. Published by Elsevier Taiwan LLC.