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.

Antidiabetic effects of a lipophilic extract obtained from flowers of Wisteria sinensis by activating Akt/GLUT4 and Akt/GSK3β

“…Detailed methods of cell culture and glucose uptake test were consistent with our previous reports (7,8). Insulin-stimulated GLUT4 and IRAP had a strong colocalization in cellular GLUT storage vesicles (GSVs).…”

“…The methods of histology and immunohistochemistry were in line with our previous reports (8). At the end of experiment, mice from all groups received retro-orbtial sinus puncture under diethyl ether anesthesia to collect blood samples.…”

“…Thus, there is a strong demand for the development of more effective and safer antidiabetic agents with limited side effects. Natural functional foods, which are characterized by safety, satisfactory effectiveness, and few side-effects, have attracted increasing interest ( 7 , 8 ). Previous reports have shown that several functional foods, such as bitter gourd, avocado pear, and broccoli, have remarkable antidiabetic effects ( 9 – 11 ).…”

“…Currently, the GLUT4 translocation assay system based on L6 cells with stable over-expression of insulin-responsive aminopeptidase (IRAP)-mOrange has been established. This system has been used for screening potential antidiabetic agents among foods (7,8,17,18). Based on the bioassay method, a lipophilic extract from the flowers of W. sinensis (WS-PE) was found to positively stimulate GLUT4 translocation and increase glucose uptake.…”

Antidiabetic Activity of a Flavonoid-Rich Extract From Sophora davidii (Franch.) Skeels in KK-Ay Mice via Activation of AMP-Activated Protein Kinase

“…The mixture was lysed for 30 min on ice, and centrifuged at 12,000 g for 15 min at 4°C, whereby non soluble material was discarded, and the protein concentration was measured as described above. Collected proteins in cells and tissues were subjected to western blot analysis according to the methods described previously ( Huang et al, 2016 ; Yang et al, 2017 ). Briefly, an equivalent amount of samples were subjected to 8 or 10% sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and transferred to a polyvinylidene difluoride membrane (Pall Corporation, Washington, United States), and the membranes were incubated with primary antibodies and HRP-conjugated secondary antibodies.…”