Activity of Isoliensinine in Improving the Symptoms of Type 2 Diabetic Mice via Activation of AMP-Activated Kinase and Regulation of PPARγ.

ABSTRACT

This study was designed to explore the effects and mechanism of isoliensinine (isolie) from embryos of Nelumbo nucifera on type 2 diabetes and dyslipidemia in vivo and in vitro. The in vitro study showed that isolie increased the GLUT4 translocation by 2.5-fold in L6 cells. Furthermore, after 4 weeks of treatment, the in vivo biochemical study indexes revealed that isolie had a positive effect on decreasing serum insulin level (42.2 ± 5.10 vs 55.7 ± 6.33 mU/L, P < 0.05) and reducing fast blood glucose (9.4 ± 1.5 vs 18.7 ± 2.3 mmol/L, P < 0.001) and body weight (37.8 ± 2.9 vs 46.9 ± 5.4 g, P < 0.05) compared with the KK-Ay model mice. Isolie treatment led to significant increases in GLUT4 proteins (∼2.7-fold in skeletal muscle and ∼2.4-fold in WAT) and phosphorylated AMP-activated protein kinase (∼1.4-fold in skeletal muscle, ∼3.1-fold in WAT, and ∼2.3-fold in liver). However, isolie caused a significant decrease in lipogenesis protein expressions of PPARγ and SREBP-1c, and decreased the activity of ACC by increasing the phospho-ACC level. Our findings showed that isolie has the potential to alleviate type 2 diabetes associated with hyperlipidemia in KK-Ay mice. Regulation of GLUT4, SREBP-1c, PPARγ, AMPK phosphorylation, and ACC phosphorylation is implicated in the antidiabetic effects of isolie.