October - December 2013, Volume 9, Issue 4

Yang G, Chen S, Ding P, Jiang G, Fu C, Hu G, Feng X, Zhu W

Pioglitazone Improves Insulin Sensitivity in Insulinresistant KKAy Mice: Involvement of a PPAR?-Dependent Signaling Pathway

Acta Endo (Buc) 2013, 9 (4): 515-524
doi: 10.4183/aeb.2013.515

Aim. To explore the effects and underlying mechanisms of pioglitazone (pio) on insulin sensitivity in insulin-resistant KKAy mice. Methods. Sixteen eight-week-old male KKAy mice were randomly assigned to two groups based on body weight: an insulin resistance model group and a pioglitazone treatment group (hereafter referred to as the pio-group). Eight male C57BL/6J mice were used as an insulin resistance control group. Mice in all three groups were fed an AIN-93G diet, and pio was added to the diet in the pio-group. After twelve weeks of treatment, blood glucose, serum insulin, glucose tolerance, and insulin tolerance were measured. ELISA was used to determine adiponectin and leptin in serum. A real time PCR assay was used to detect the mRNA of adiponectin and leptin in epididymal adipose tissue. A Western blot assay was used to analyze protein expression and/ or phosphorylation levels of peroxisome proliferator activated receptor γ (PPARγ), insulin receptor substrate 1 (IRS1), and protein kinase B (PKB/AKT) in the liver and epididymal adipose tissue.Results. The results showed that Pio treatment may effectively reduce levels of blood glucose and serum insulin, improve insulin tolerance and glucose tolerance, increase serum adiponectin, decrease serum leptin, and enhance mRNA expression of adiponectin in epididymal adipose tissue. Furthermore, with pio treatment, protein expression of PPARγ and phosphorylation levels of IRS1 and AKT were increased in the liver and epididymal adipose tissue. Conclusion. These results suggested that Pio intervention may ameliorate insulin resistance and improve insulin sensitivity in KKAy mice, which may be due to an increase of PPARγ and further activation of the insulin signaling transduction pathway (IRS1 and AKT) in the liver and epididymal adipose tissue of KKAy mice.

Keywords: Pioglitazone, insulin resistance, PPAR?, IRS1, AKT.

Correspondence: Wei Zhu MD, Gaungzhou Center for Disease Control and Prevention - Toxicology, No.1, Qide Road, Baiyun District, Guangzhou, 510440, China, E-mail: zhuyc126@126.com