br Materials and methods br Results br

Materials and methods
Results
Discussions Diabetes is mainly divided into Type 1 diabetes and Type 2 diabetes [16]. Type 2 diabetes, featured by insulin resistance, results from environmental factors and poor eating habits [2]. Type 2 diabetes accounts for more than 95% of the diabetic patients and the incidence is increasing year by year. The current clinical treatment of type 2 diabetes is the short-term control of blood sugar and the long-term prevention of complications. There are many clinical hypoglycemic agents. Short-term treatment with these agents can effectively control blood glucose level and improve the state of insulin resistance, but long-term treatment with these agents will have serious side effects, such as persistent hypoglycemia, lactic acidosis, liver damage and other serious adverse even life-threatening reactions. In recent years, some progress has been achieved in the daily application of botanical supplements in the prevention and treatment of diabetes and its complications [17]. Many researches have reported that VA can reduce fasting blood glucose in type 2 diabetic mice and improve insulin resistance. VA may have a hypoglycemic effect by up-regulating GLUT4 in the skeletal muscle [18] and potentiating glucose oxidation via the pentose phosphate pathway [15]. VA also could promote glycolytic enzymes. Our results indicated that the administration of VA effectively reduces fasting blood glucose levels, improves oral glucose tolerance and insulin resistance in the mice with type 2 diabetes. These results are consistent with previous reports [19,20]. Liver plays a major role in glycolipid metabolism [21]. In the developmental process of many metabolic diseases, the regulation of liver is particularly important. Previous researches have shown that hepatic gluconeogenesis is an important part of glycogen metabolism because it can maintain the Azimilide or the body in a steady state [22]. In short, when body is in fasting or hunger, liver will enhance glycogenolysis and inhibit glycogen synthesis, but glycogen is limited. Glucose by glycogenolysis will be used up after the meal for 12 h. To maintain a constant blood glucose level, liver will enhance hepatic gluconeogenesis. Researches have shown that liver gluconeogenesis disorders are closely related to diabetes, obesity, nonalcoholic fatty liver and other insulin resistance diseases. When type 2 diabetes occurs, it causes peripheral insulin resistance and relatively insufficient insulin secretion. The inhibition effect of insulin on hepatic glucose output will be weakened, leading to abnormal glucose and lipid metabolism, ultimately producing elevated blood sugar [23]. Inhibiting excessive hepatic gluconeogenesis can be considered as a therapeutic target in type 2 diabetes. The results of this research in vitro and in vivo indicated that VA has an inhibitory effect of hepatic gluconeogenesis. The suppression of VA on gluconeogenesis partially contributes to the reduction of fasting blood glucose level and the improvement of insulin resistance. Therefore, VA might be a promising therapeutic drug for type 2 diabetes. PEPCK and G6Pase are rate-limiting enzymes of gluconeogenesis. They are important in regulating the hepatic glucose production [22]. Researches have shown that the expression of PEPCK and G6Pase proteins have abnormally increased in Type 2 diabetes. So inhibiting the expression of PEPCK and G6Pase proteins is crucial in the treatment of diabetes. Our research results showed that VA reduced gluconeogenesis by down-regulating the levels of PEPCK and the G6Pase proteins not only in PA-induced HepG2 cells but also in STZ-induced type 2 diabetes mice. We also observed that VA decreased glucose production in insulin-resistant HepG2 cells induced by PA. Therefore, our results indicated that the glucose-lowering effect induced by VA at least partially through the suppression of hepatic gluconeogenesis, which agree with the results of a previous research [15].