Abstract
Aim: To investigate the anti-diabetic activity of amentoflavone (AME) in diabetic mice, and to explore the potential mechanisms. Methods: Diabetic mice induced by high fat diet and streptozotocin were administered with amentoflavone for 8 weeks. Biochemical indexes were tested to evaluate its anti-diabetic effect. Hepatic steatosis, the histopathology change of the pancreas was evaluated. The activity of glucose metabolic enzymes, the expression of Akt and pAkt, and the glucose transporter type 4 (GLUT4) immunoreactivity were detected. Results: AME decreased the level of glucose, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and glucagon, and increased the levels of high density lipoprotein cholesterol (HDL-C) and insulin. Additionally, AME increased the activity of glucokinase (GCK), phosphofructokinase-1 (PFK-1), and pyruvate kinase (PK), and inhibited the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G-6-Pase). Mechanistically, AME increased superoxide dismutase (SOD), decreased malondialdehyde (MDA), activation of several key signaling molecules including pAkt (Ser473), and increased the translocation to the sedimenting membranes of GLUT4 in skeletal muscle tissue. Conclusions: AME exerted anti-diabetic effects by regulating glucose and lipid metabolism, perhaps via anti-oxidant effects and activating the PI3K/Akt pathway. Our study provided novel insight into the role and underlying mechanisms of AME in diabetes.
Highlights
Diabetes mellitus is a complex, heterogeneous, and polygenic disease which is characterized by increasing circulating glucose concentrations associated with abnormalities in carbohydrate, protein and fat metabolism caused by the complete or relative insufficiency of insulin secretion and/or insulin action
The diabetic control group (DC) mice led to an over five-fold elevation of the blood glucose level compared with the normal control group (NC) mice (p < 0.01)
Insulin resistance and insufficiency of insulin secretion are the basis of type 2 diabetes [6]
Summary
Diabetes mellitus is a complex, heterogeneous, and polygenic disease which is characterized by increasing circulating glucose concentrations associated with abnormalities in carbohydrate, protein and fat metabolism caused by the complete or relative insufficiency of insulin secretion and/or insulin action. Treatment of diabetes mellitus involves diet control, exercise and the use of insulin and/or oral hypoglycemic drugs. Many oral hypoglycemic agents have a number of serious adverse effects [2]. The adverse reactions limit the use of antidiabetic drugs. Looking for new antidiabetic drugs which have little adverse reaction appears to be very urgent. Traditional and natural indigenous medicines on diabetes prevention and treatment have become a research focus, and a large number of natural plants/plant products have been evaluated for their anti-diabetic effects [3]
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