The Effects Of EGb761 On Islet Function In Db/db Mice

Backgroud:Although modern medicine to the understanding of the pathogenesis and treatment of type 2 diabetes has made significant progress, but its prevalence is still high.The clinical incidence of type 2 diabetes in our country presents the trend of rising and younger, the disease has become one of the basic diseases that extremely adverse effects on the population in our country especially middle-aged and old people,in the face of this growing prevalence of permanent disease, we not only need to strengthen the basic and applied research, but also constantly explore and innovate the diagnosis and treatment of diabetes. Ginkgo is one of China’s ancient tree species, its extract EGb761 (Ginkgo biloba extract 761, EGb761) is recognized as a powerful antioxidant, has been proved that it can clear oxygen free radicals,inhibit the generation of NO, relax vascular smooth muscle, reduce the peripheral blood flow resistance, increase local blood flow, improve cardio-cerebral blood circulation, it is a kind of drugs that has been commonly used in the treatment of ischemic cardio-cerebrovascular disease at home and abroad, in the clinical and basic researches of heart cerebrovascular disease with diabetes mellitus in clinical and basic research, some scholars found EGb761 can significantly improve the blood glucose levels, protect islet beta cells, which provides a new therapy for the treatment of diabetes, but the mechanism is not yet clear, in our experiment we take the db/db mice aged 8 weeks as the model, through determining oxidation markers in the body to explore EGb761 affect islet secretion and possible mechanismsMethods:1、Ten db/db mice aged 8 weeks were randomized to EGb761 group and db/db group,fed with EGb761 100 mg/(kg-d) and placebo respectively. Five age-matched db/misty mice were concurrently treated with placebo as non-diabetic control group.2、Body weight and random blood glucose were measured every week. Before drug delivery and after 8 weeks’treatment, fasting blood glucose、 fasting insulin were determined. Aslo we should calculate the area under curve of glucose and insulin and insulin sensitive index, after 8 weeks’ drug delivery,we take Intraperitoneal glucose tolerance test in 5 mice of each group, With insulin area under the curve (AUCFSI) evaluation islet secretion, with 0-30 min insulin area under the curve (AUCFSIO-30) to evaluate the early phase of insulin secretion.3、Compare the body weight, fasting glucose, fasting insulin, glucose tolerance, insulin secretion,nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression level in pancreatic islet, strength of insulin dyeing, islet beta cells before and after 8 weeks’drug delivery.Results:1、 Comparison of body weight, fasting glucose, fasting insulin, insulin sensitive index:before drug delivery, EGb761 and db/db group had no difference between the weight and blood sugar;after eight weeks’ treatment the body weight still there had no significant difference in both groups, but EGb761 group had a significantly lower fasting glucose than db/db group (p< 0.05), and insulin sensitive index increased significantly.2、Comparison of intraperitoneal glucose tolerance test:before sugar load and after 30,60,120 min, blood sugar and glucose area under curve of EGb761 group significantly reduced than db/db group, the difference were statistically significant. Sugar load after 30 min, plasma insulin levels of EGb761 group rose, and AUCFSI0-30 was significantly higher than db/db group (P<0.05).3、Comparison of insulin staining intensity, islet beta cells number: compared with the db/m group, the pancreas insulin staining intensity within db/db group decreased obviously (P<0.05),but the intensity of insulin dyeing、the number of islet beta cells in EGb761 group were significantly higher than that of db/db group, which between the db/m group and the db/db group (P< 0.05).4、Comparison of NADPH oxidase expression in pancreas:Gp91phox and p22phox positive area appeared in the islet cell cytoplasm, semi-quantitative analysis showed that the expression of Gp91phox and p22phox were the strongest in db/db group,treatment with EGb761 significantly reduced Gp91phox and p22phox expression intensity even close to the db/m group’s level (P< 0.001).Conclusions:1、Before and after the test,EGb761 has no obvious effect on body weight in mice, but can reduce fasting blood glucose,rose insulin sensitivity index, improve glucose tolerance and the secrete function of islet beta cells, especially in the early phase of insulin secretion, all of these explaine that EGb761 has certain protective effect on diabetes.2、Comparison of the strength of insulin dyeing、islet beta cells number before and after the text, it prompted that EGb761’s effect on diabetes maybe act by increasing islet mass, protecting insulin secretion function of islet beta cells and so on.3、After intervention of EGb761,the espression strength of gp91phox and p22phox in NaDPH oxidase significantly reduced,it prompted that the possible mechanism of EGb761 on diabetes is realized by reducing islet oxidative stress level.