Hepatosteatosis and hepatic insulin resistance are blunted by argirein, an anti-inflammatory agent, through normalizing endoplasmic reticulum stress and apoptosis in diabetic liver

• Published in: Journal of pharmacy and pharmacology 2013-06, Vol.65 (6), p.916-927
• Main Authors: Shi, Fang-Hong, Wu, You, Dai, De-Zai, Cong, Xiao-Dong, Zhang, Yu-Mao, Dai, Yin
• Format: Article
• Language: English
• Subjects: Animals; Anthraquinones - pharmacology; Anti-Inflammatory Agents - pharmacology; apoptosis; Apoptosis - drug effects; Arginine - pharmacology; argirein; Cells; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diet, High-Fat - adverse effects; Drug Combinations; eIF-2 Kinase - metabolism; Endoplasmic Reticulum Stress - drug effects; ER stress; Glucose - metabolism; Glucose Transporter Type 4 - metabolism; GluT4; Glutathione Peroxidase - blood; Glutathione Peroxidase - metabolism; Glycogen - metabolism; Heat-Shock Proteins - metabolism; hepatosteatosis; Insulin - blood; Insulin - metabolism; Insulin Receptor Substrate Proteins - metabolism; Insulin resistance; Insulin Resistance - physiology; IRS-1; Liver - drug effects; Liver - metabolism; Lymphoma; Male; PPAR alpha - metabolism; PPAR gamma - metabolism; Proteins; Rats; Rats, Sprague-Dawley; Receptors, Leptin - metabolism; Rodents; Tetrazoles - pharmacology; Transcription Factor CHOP - metabolism; Valine - analogs & derivatives; Valine - pharmacology; Valsartan
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.12051

Objectives Insulin resistance represents a mechanism underlying defect metabolism of carbohydrate and lipid linked to inflammatory reactions in diabetic liver. We hypothesized that the changes may be secondary to endoplasmic reticulum (ER) stress, which could be alleviated by either argirein or valsartan. Methods Hepatosteatosis in diabetic liver was induced in rats fed with a high‐fat diet (HFD) for 12 weeks combined with a single low dose of streptozotocin (STZ 35 mg/kg, ip). Interventions (mg/kg/d, po)with either argirein (50, 100 and 200) or valsartan (12) were conducted in the last 4 weeks. Key findings In diabetic liver fat was significantly accumulated in association with elevated hepatic glucose, serum insulin and homeostasis model assessment of insulin resistance value. Downregulated glucose transporter 4, insulin receptor substrate‐1 and leptin receptor (P