tiliroside and Insulin-Resistance

We explored the effects of tiliroside derivatives on cell surface GLUT4 level (GLUT4 translocation) and the underlying mechanism in L6-GLUT4. We showed that tiliroside derivatives D1-22 stimulated GLUT4

Topics: AMP-Activated Protein Kinases; Animals; Cells, Cultured; Flavonoids; Glucose Transporter Type 4; GTPase-Activating Proteins; Insulin Resistance; Muscle, Skeletal; Protein Transport; Rats

In our previous study, a derivative of tiliroside, 3-O-[(E)-4-(4-ethoxyphenyl)-2-oxobut-3-en-1-yl]kaempferol (Fla-OEt) significantly enhanced glucose consumption in insulin resistant HepG2 cells. This article deals with the antihyperglycemic and antihyperlipidemic effects of Fla-OEt in diet-induced obesity (DIO) mice. Daily administration of Fla-OEt significantly decreased oral glucose tolerance test, intraperitoneal insulin tolerance test and serum lipids. Hyperinsulinemic-euglycemic clamp and the ratio of high-density-lipoprotein/low-density-lipoprotein with Fla-OEt treatment were increased comparing with high-fat diet (HFD) group, so lipid metabolism was improved. Histopathology examination showed that the Fla-OEt restored the damage of adipose tissues and liver in DIO mice. Moreover, compared with HFD group, Fla-OEt treatment significantly increased the phosphorylation of AMPK and ACC in adiposity tissues, liver, and muscles. The mechanism of its action might be the activation of AMPK pathway. It appears that Fla-OEt is worth further study for development as a lead compound for a potential antidiabetic agent.

Topics: Adipose Tissue; AMP-Activated Protein Kinases; Animals; Diet, High-Fat; Flavonoids; Hypoglycemic Agents; Insulin Resistance; Lipid Metabolism; Liver; Male; Mice; Mice, Obese; Obesity; Phosphorylation

A set of novel trans-tiliroside derivatives were synthesized. The structures of the derivatives were identified by their IR, 1H-NMR, and MS spectra analysis. Their anti-diabetic activities were evaluated on the insulin resistant (IR) HepG2 cell model. As a result, compounds 7a, 7c, 7h, and trans-tiliroside exhibited significant glucose consumption-enhancing effects in IR-HepG2 cells compared with the positive control (metformin). This research provides useful clues for further design and discovery of anti-diabetic agents.

Topics: Flavonoids; Glucose; Hep G2 Cells; Humans; Hypoglycemic Agents; Insulin Resistance; Magnetic Resonance Spectroscopy; Metformin; Models, Biological; Molecular Structure