Literature DB >> 15842776

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

Shi-ying Ding1, Zhu-fang Shen, Yue-teng Chen, Su-juan Sun, Quan Liu, Ming-zhi Xie.   

Abstract

AIM: To investigate the effect of the peroxisome proliferator-activator receptor (PPAR)-gamma agonist, pioglitazone, on insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats.
METHODS: Normal female Wistar rats were injected intraperitoneally with low-dose streptozotocin (STZ, 30 mg/kg) and fed with a high sucrose-fat diet for 8 weeks. Pioglitazone (20 mg/kg) was administered orally to the obese and insulin-resistant rats for 28 d. Intraperitoneal glucose tolerance tests, insulin tolerance tests and gluconeogenesis tests were carried out over the last 14 d. At the end of d 28 of the treatment, serums were collected for biochemical analysis. Glucose transporter 4 (GLUT4) and insulin receptor substrate-1 (IRS-1) protein expression in the liver and skeletal muscle were detected using Western blotting.
RESULTS: Significant insulin resistance and obesity were observed in low-dose STZ and high sucrose-fat diet induced obese rats. Pioglitazone (20 mg/kg) treatment significantly decreased serum insulin, triglyceride and free fatty acid levels, and elevated high density lipoprotein-cholesterol (HDL-C) levels. Pioglitazone also lowered the lipid contents in the liver and muscles of rats undergoing treatment. Gluconeogenesis was inhibited and insulin sensitivity was improved markedly. The IRS-1 protein contents in the liver and skeletal muscles and the GLUT4 contents in skeletal muscle were elevated significantly.
CONCLUSION: The data suggest that treatment with pioglitazone improves insulin sensitivity in low-dose STZ and high sucrose-fat diet induced obese rats. The insulin sensitizing effect may be associated with ameliorating lipid metabolism, reducing hyperinsulinemia, inhibiting gluconeogenesis, and increasing IRS-1 and GLUT4 protein expression in insulin-sensitive tissues.

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Year:  2005        PMID: 15842776     DOI: 10.1111/j.1745-7254.2005.00090.x

Source DB:  PubMed          Journal:  Acta Pharmacol Sin        ISSN: 1671-4083            Impact factor:   6.150


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