Pioglitazone can ameliorate insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats

Aim:To investigate the effect of the peroxisome proliferator-activator receptor(PPAR)-γ agonist,pioglitazone,on insulin resistance in low-dose streptozotocinand high sucrose-fat diet induced obese rats.Methods:Normal female Wistar ratswere injected intraperitoneally with low-dose streptozotocin(STZ,30 mg/kg)andfed with a high sucrose-fat diet for 8 weeks.Pioglitazone(20 mg/kg)was adminis-tered orally to the obese and insulin-resistant rats for 28 d.Intraperitoneal glu-cose tolerance tests,insulin tolerance tests and gluconeogenesis tests were car-ried out over the last 14 d.At the end of d 28 of the treatment,serums werecollected for biochemical analysis.Glucose transporter 4(GLUT4)and insulinreceptor substrate-1(IRS-1)protein expression in the liver and skeletal musclewere detected using Western blotting.Results:Significant insulin resistance andobesity were observed in low-dose STZ and high sucrose-fat diet induced obeserats.Pioglitazone(20 mg/kg)treatment significantly decreased serum insulin,triglyceride and free fatty acid levels,and elevated high density lipoprotein-cho-lesterol(HDL-C)levels.Pioglitazone also lowered the lipid contents in the liverand muscles of rats undergoing treatment.Gluconeogenesis was inhibited andinsulin sensitivity was improved markedly.The IRS-1 protein contents in the liverand skeletal muscles and the GLUT4 contents in skeletal muscle were elevatedsignificantly.Conclusion:The data suggest that treatment with pioglitazoneimproves insulin sensitivity in low-dose STZ and high sucrose-fat diet inducedobese rats.The insulin sensitizing effect may be associated with amelioratinglipid metabolism,reducing hyperinsulinemia,inhibiting gluconeogenesis,and in-creasing IRS-1 and GLUT4 protein expression in insulin-sensitive tissues.