| ObjectivesBiotin is an essential co-enzyme for human, it is a cofactor for four carboxylase enzymes, which is closely associated with the metabolism of glucose and lipid. Because human body can synthesize biotin by intestinal bacteria, biotin deficiency is very rare in the population, unless there is a defection in the congenital gene. As a result, there were relatively few studies on biotin, it became the "forgotten" vitamin. But in recent years, along with the development of biological technology and research, researchers found that biotin can affect the multiple gene expression and regulate the downstream events as well as the regulation of blood glucose through histone biotinylation. Also there are some studies that demonstrate that the large doses of biotin and chromium picolinate combination can significantly lower blood sugar levels in patients with diabetes. However there still exists some controversy for the separate role of biotin in regulating the blood glucose or lipid, therefore we hope through this study on rats with different blood glucose, to explore the effect of biotin on blood sugar regulation in rats and its possible mechanism.MethodsPhase Ⅰ:The effect of biotin on glucose regulation in impaired glucose tolerance rats.According to initial body weight and blood sugar, we randomly divided the 110 Wistar rats into six groups, there are respectively the normal control group, model group, chromium picolinate group (0.2mg/kg.BW), biotin low-dose group (0.6mg/kg.BW), biotin medium-dose group (3.0mg/kg.BW) and biotin high-dose group (6.0mg/kg.BW).The normal group was given the normal feed for maintenance, the others HFS diet. We did OGTT experiment on the 8th week and 12th week respectively, calculated the area under the blood glucose response curve (AUC) and measured the triglycerides and total cholesterol.Phase Ⅱ:The effect of biotin on glucose regulation of diabetic ratsAt the 13th week, the rats with HFS feed were injected with STZ (25mg/kg.BW) to manufacture diabetic rat model. Suspended the gavaging of biotin and chromium picolinate for one week, then restore the normal administration; we observed the rat intake and weight change Closly. At the 15th week, after the rats blood sugar becomed stable, measured the fasting blood glucose and blood glucose two hours after meals, at the same time, measured the serum content of biotin.At the 23th week we did the OGTT experiment, and ended the experiment at 25th week. We detected the blood glucose, insulin, TC, TG, liver/muscle glycogen and other biochemical indexes; Weighted the liver, kidney, heart and pancreas, and performed the pathological examination; Rapidly freezing another sample of liver, muscle, kidney and spleen in liquid nitrogen; Measured the GLUT4, PI3K, FoxO1, PPAR y mRNA expression in the PI3K/AKT signaling pathway through RT-PCR method.ResultsBiotin has a certain degree of improvement on post-prandial glucose in impaired glucose tolerance rats. After 12 weeks of biotin intervention, compared with the model group, the AUC of biotin medium-dose group was significantly decreased (P<0.05); the 2-hour post-prandial blood glucose of biotin high-dose group was significantly decreased (P<0.05).Biotin has a certain improvement on postprandial glucose in diabetic rats. Compared with the model group, the AUC and the 30min postprandial blood glucose of biotin high-dose group were significantly decreased (P<0.05).Biotin can alleviate the effects of fatty liver in diabetic rats. There is severe fatty liver in diabetic rats, liver function indexes all raised. Compared with the model group, biotin significantly improved the ALT、 AST and ALP of diabetic rats (P<0.05). Hematoxylin-eosin staining also showed biotin significantly reduced liver steatosis. Insulin immune histone-chemical staining showed that the biotin can protect the pancreatic tissue and increase the number of islet beta cell. Biotin can affect the GLUT4,IR, PI3K, FoxO1 gene expression in PI3K/AKT signaling transduction pathway; And biotin also affect some key enzyme gene in glucose metabolism, such as GCK, PCK1, Pcca, Pccb; energy metabolism gene UCP1 and fat metabolism gene UCP2、Fasnand PPARγConclusionBiotin can effectively inhibit the PBG of impaired glucose tolerance rats. Biotin can improve the PBG of type 2 diabetic rats excellently. In addition, biotin can improve the muscle glycogen mobilization protect pancreatic tissue、increase the number of islet β cell sin diabetic rats, and has protective effect on the liver. The possible mechanism of the decreasing biotin blood sugar in diabetic rats may by improving the insulin sensitivity through affecting PI3K/AKT signal transduction pathway, as well as promoting the synthesis of glycogen and reducing gluconeogenesis. |
PDF Full Text Request