Taurine prevents free fatty acid-induced hepatic insulin resistance in association with inhibiting JNK1 activation and improving insulin signaling in vivo.
We infused the 48 h intralipid plus heparin (IH) to normal rats to elevate plasma free fatty acids (FFAs). Co-infusion of taurine was designed for the purpose of studying the effects of taurine on insulin sensitivity, oxidative stress, c-Jun NH-terminal kinase (JNK)1 activity and insulin signaling in livers of prolonged IH-infused rats. Cannulated rats were infused for 48 h intravenously with either saline or IH, with or without taurine. Hyperinsulinemic-euglycemic clamps with [6-3H] glucose infusion were performed to assess hepatic insulin sensitivity. IH infusion increased plasma 8-isoprostaglandin and hepatic malondialdehyde (MDA). IH also increased JNK1 activity and insulin receptor substrate 1/2 (IRS-1/2) serine phosphorylation, reduced insulin-stimulated IRS-1/2 tyrosine phosphorylation and Akt serine 473 phosphorylation, and induced hepatic insulin resistance. Taurine co-infusion with IH prevented the rise in 8-isoprostaglandin and MDA, inhibited the activation of JNK1, and improved insulin signaling and insulin resistance in liver. The present study has demonstrated that taurine, as an antioxidant, prevented hepatic oxidative stress and ameliorated hepatic insulin resistance. And this effect may be associated with the inhibition of JNK1 activation and the improvement of insulin signaling. This study suggests the therapeutic value of taurine in protecting from hepatic insulin resistance caused by elevated FFAs.
Wu
Na
N
Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Lu
Yan
Y
He
Bing
B
Zhang
Yongyan
Y
Lin
Jingfeng
J
Zhao
Sheng
S
Zhang
Wei
W
Li
Yan
Y
Han
Ping
P
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004655:Emulsions / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008314:Malonates / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000187:drug effects; D010743:Phospholipids / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013024:Soybean Oil / Q000494:pharmacology; D013654:Taurine / Q000494:pharmacology*
D000975:Antioxidants; D004655:Emulsions; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D008314:Malonates; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D013654:Taurine; D013024:Soybean Oil; D006493:Heparin; C030290:malonic acid; D051057:Proto-Oncogene Proteins c-akt; D048055:Mitogen-Activated Protein Kinase 8