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

Abstract

Background: Type 2 diabetes mellitus is primarily caused by insulin resistance (IR) in insulin-sensitive tissues, including liver, white adipose tissues (WAT), and skeletal muscles. Discovering nutritious foods with antidiabetic effects is of great significance. Numerous published reports indicated that protein kinase B (Akt) and glucose transporter 4 (GLUT4) play crucial roles in ameliorating IR and diabetic symptoms. Objective: In the present study, antidiabetic effects and the potential mechanism of action of WS-PE (a lipophilic extract from edible flowers of Wisteria sinensis) were explored with L6 cells in vitro and in high-fat diet (HFD) + Streptozocin (STZ)-induced diabetic mice in vivo. Design: In vivo, HFD + STZ-induced diabetic mice were used as diabetic models to investigate the potential antidiabetic and antidyslipidemic activities. In vitro, a novel GLUT4 translocation assay system was established to evaluate the potential effects of WS-PE on GLUT4 translocation. Western blot analysis was adopted to investigate the molecular mechanisms of WS-PE both in vivo and in vitro. Results: In vitro, WS-PE increased glucose uptake by stimulating GLUT4 expression and translocation, which were regulated by Akt phosphorylation. In vivo, the WS-PE treatment ameliorated the hyperglycemia, IR, and dyslipidemia and reversed hepatic steatosis and pancreatic damage in diabetic mice. The WS-PE treatment increased GLUT4 expression by Akt activation in WAT and skeletal muscle. Akt activation stimulated GSK3β phosphorylation in liver and skeletal muscles, indicating that WS-PE showed regulatory effects on glycogen synthesis in liver and skeletal muscles. Conclusion: These in vitro and in vivo results indicated that the WS-PE treatment exerted antidiabetic effects by activating Akt/GLUT4 and Akt/GSK3β.

Glucose metabolism enhancement by 10-hydroxy-2-decenoic acidviathe PI3K/AKT signaling pathway in high-fat-diet/streptozotocin induced type 2 diabetic mice

“…Type 2 diabetes mellitus (T2DM) is the most prevalent form of diabetes, accounting for 90% of diabetes cases, 1 and is characterized by hyperglycemia and insulin deficiency caused by β-cell dysfunction and insulin resistance (IR) in various target organs, including the liver, heart, skeletal muscle, and adipose tissue. [2][3][4][5][6] After a meal, insulin secreted from the pancreas triggers a systemic metabolic response involving the joint efforts of insulin target tissues, including the liver, muscle, and adipose tissues. 7 High blood glucose levels in tissues with active redox cellular functions lead to generation of reactive oxygen species (ROS), which causes oxidative stress damage, particularly in the liver, pancreas, and kidney.…”

Effects of Root Extract of Morinda officinalis in Mice with High-Fat-Diet/Streptozotocin-Induced Diabetes and C2C12 Myoblast Differentiation

“…A high-calorie diet and obesity are the main risk factors for T2DM. , In the present study, HFD-fed mice showed an increase in body weight, induction of both insulin resistance, and glucose tolerance that may mimic the human lifestyle. − Streptozotocin is selectively toxic to the insulin-producing β cells of the pancreas in mammals and has been long injected in experimental animals for the reproduction of diabetes pathology in humans . Multiple methods of STZ dosing depend on the type and the severity of diabetes in mice, and the dose range also varies largely, so they are applied in various ways from 100 to 200 mg/kg in a single high dose.…”

Chemical Constituents from Roots of Sophora davidii (Franch.) Skeels and Their Glucose Transporter 4 Translocation Activities

“…Zen 2010 Software (Carl Zeiss, Jena, Germany) was used to analyze the fluorescence intensity of mOrange. The detailed method of GLUT-4 fusion with the plasma membrane was described in previous reports [ 24 ].…”