Hypoglycemic Activity Of Cinnamon Polyphenol And Its Mechanism

Diabetes is a metabolic disease as a result of absolute insufficient of insulin secretion or of reducing response to insulin. Now, it has been one of 3 types of serious illness they are diabetes,cardiovascular and cerebrovascular disease and tumor and is a serious harm to human health, moreover it is characteristic of high morbidity,a long course of disease, complex pathogenetic condition and being difficult to cure, and so on. At present it is treated mainly by Western medicine which has exact therapeutic effect, but Western medicine has side effects and form―treatment refractoriness‖after using medicine for a long time. The hypoglycemic effect of Chinese medicine has pharmacological characteristics of multi-channel, multi-target, multi-dimensionality; moreover the hypoglycemic effect is moderate and persistent and can delay the complications, and so on.Objective: To investigate the hypoglycemic activity of polyphenols extracted from cinnamon by the insulin-resistant diabetes mice and HepG2 cells and further study its mechanism of the hypoglycemic effect.Methods: Diabetes rats were induced by high-fat diet-fed and intraperitoneal (ip) injection of streptozotocin ,then these rats were used to investigate the hypoglycemic effect of cinnamon polyphenols, Diabetic mice were divided into control group,cinnamon polyphenols treatment group (100,200,300mgkg-1d-1) and positive control metformin group (500 mgkg-1d-1), all the groups were intragastric administration. After two weeks they were measured in body weight and blood glucose concentration; The effect of cinnamon polyphenols on viability of HepG2 cells was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylterazolium bromide (MTT) assay; At the same time, insulin resistance cell model was induced by high concentrations insulin, the hypoglycemic effect of cinnamon polyphenols in HepG2 cells was detected; to detect the activity of PEPCK and GK by 6 - phosphate glucose dehydrogenase coupling colorimetric method and lactate dehydrogenase coupling colorimetric method; The real time RT-PCT analysis was performed to detect the effect of cinnamon polyphenols on some key gene expression in relation to glucose metabolism in HepG2 cells, including the insulin receptor (IR),glucose transporter GLUT2 that regulating glucose conveying in the body,The key rate-limiting enzyme in the pathway of gluconeogenesis: Phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase). Results: Animal models of diabetes were successfully induced by high-fat diet-fed and low-dose STZ injection,there was a significantly decrease after intragastric administration of cinnamon polyphenols for two weeks compared with the model control group at the concentration of 200,300mgkg-1d-1(p<0.05), while the mice had no significant change in body weight(p>0.05); At the concentrations (1-15μg/ml), the cinnamon polyphenols had no depressant effect on the cells activity; Cinnamon polyphenols could significantly promote extracellular glucose consumption in the HepG2 cells and the insulin-resistant HepG2 cells(p<0.05,p<0.01), moreover, with the increase of concentration, Cinnamon polyphenols had more apparent hypoglycemic effect; At the concentration of 15μg/ml, Cinnamon polyphenols could enhance the GK activity of the insulin resistance HepG2 cells(p<0.05), and at the concentration of 10μg/ml,15μg/ml, Cinnamon polyphenols could significantly suppress PEPCK activity (p<0.05,p<0.01); At the same time, Cinnamon polyphenols could significantly inhibit expression of GLUT2mRN,phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) mRNA in the pathway of gluconeogenesis (p<0.05,p<0.01);But the mRNA of IR had no obviously change).Conclusion: Animal models of diabetes were successfully induced by high-fat diet-fed and low-dose STZ injection; Cinnamon polyphenols could significantly reduce blood glucose levels in the diabetic mice after intragastric administration. At a cellular level, cinnamon polyphenols could significantly promote extracellular glucose consumption in the HepG2 cells and the insulin-resistant HepG2 cells,significantly enhance the cell sensitivity to insulin of the low concentration and improve the insulin-resistant state, thus in a certain , to prevent or reverse insulin resistance development. Cinnamon polyphenols could suppress the gluconeogenesis and reduce the cell endogenous glucose production by inhibiting the gene expression of PEPCK and G6Pase and the activity of PEPCK; besides to promote the using of cell for the glucose by promoting the activity of GK and the expression of adjusting GLUT2mRNA in HepG2 cells,so cinnamon polyphenols improve the insulin resistance .