Traditional Chinese Medicine Compound Sugar Resistant To The Treatment Of Clinical Abnormal Glucose Tolerance And Insulin Resistance Mechanism Research

Abnormal glucose tolerance (IGT) is a human disorder of carbohydrate metabolism in compensatory stage, and it is also a transition stage from normal to diabetes. The prevention and treatment of which is a research hotspot at present. The research evaluated the clinical effectiveness of Tang NaiKang (TNK) in treating IGT by clinical research, and also tried to look for the mechanism and target spot of TNK on intervening in glucose and lipid metabolism in hepatocyte via experimental study, the above of which provided theoretical and experimental basis for Traditional Chinese Medicine (TCM) in treating IGT.Clinical trialObjective:The project took the clinical effective Chinese herbal compound TNK as the research object, and we evaluated the clinical effectiveness of TNK intervening IGT patients through clinical research on the basis of existing research results.Materials and Methods: According to the principle of randomized, double-blind, placebo-controlled and parallel design, we randomly divided the60subjects into two groups in accordance with the proportion of3:1:the experimental group (TNK group) and the control group (Placebo group). We gave the treatment with TNK for12weeks, analyzed the baseline data, and then observed the curative effect index of2h blood glucose after meals (2hPBS) and so on.Results:Before the treatment, there were no significant differences in age, weight and height compared with A group and B group (P>0.05). There was no statistical significance in the course of disease, gender, ethnic, the source of subjects, treatment history and vital signs between the two groups before treatment (P>0.05), and the two groups were comparable. There was no statistical significance in the blood glucose, glycated hemoglobin, insulin, blood lipid and TCM syndrome integral between the two groups before treatment (P>0.05), and the two groups were comparable.PPS:Compared with B group, the changes of2hPBS in A group had statistically significant differences after the12wk treatment with TNK (P<0.05); FAS:Compared with B group, the changes of2hPBS in A group had statistically significant differences after the12wk treatment with TNK (P<0.05).Experimental studyObjeetive:The experiment studied the effect of TNK regulating the glucose and lipid metabolic disorder of hepatocyte in rats and the role of TNK regulating the AMPK signaling pathway in vitro experiments.Materials and Methods:Prepare serum containing Pioglitazone and TNK respectively. We used high glucose and palmitic acid to stimulate hepatocyte in order to cause the model of glucose and lipid metabolic disorder. Then we intervened them respectively and detected the proliferation of hepatocyte in the high glucose environment by CCK-8. At last, we used kits to detect triglycerides, glucose and glycogen.Prepare serum containing Pioglitazone and TNK respectively. We used high glucose and palmitic acid to stimulate hepatocyte in order to cause the model of glucose and lipid metabolic disorder. Then we intervened them respectively, used real-time fluorescence quantitative PCR to detect the mRNA expression of PPARa and NF-κB, and used western blot to detect the protein expression of p-JNK, JNK, p-IRS1and NF-kB.Results:Compared with the normal group, the proliferation of hepatocyte in the high glucose group was significantly inhibited (P<0.01); Compared with the high glucose group, the cell proliferation activity in pioglitazone group and in each dose group of TNK increased significantly, and the difference was statistically significant (P<0.01).The glucose consumption of hepatocyte in the high glucose group was obviously lower than the normal group (P<0.01); and the glucose consumption of hepatocyte in pioglitazone group and in each dose group of TNK increased significantly (P<0.01).Compared with the normal group, the triglyceride content of medium in the high glucose group increased significantly (P<0.01); Compared with the high glucose group, the triglyceride content of medium in each dose group of TNK decreased significantly (P<0.05). Compared with the normal group, the triglyceride content of hepatocyte in the high glucose group increased significantly (P<0.01); Compared with the high glucose group, the triglyceride content of hepatocyte in pioglitazone group and in each dose group of TNK decreased significantly (P<0.01).Compared with the normal group, the glycogen content of hepatocyte decreased significantly (P<0.01); Compared with the high glucose group, the glycogen content of hepatocyte in pioglitazone group and in each dose group of TNK increased significantly (P<0.01).Compared with the normal group, the triglyceride content of medium in the palmitic acid model group increased significantly (P<0.01); Compared with the model group, the triglyceride content of medium in pioglitazone group and in each dose group of TNK decreased significantly (P<0.01).Compared with the normal group, the glucose consumption of medium in the palmitic acid model group increased significantly (P<0.01); Compared with the model group, the glucose consumption of medium in the high dose of TNK group decreased significantly (P<0.05).Compared with the normal group, the triglyceride content of medium in the high insulin model group increased significantly (P<0.01); Compared with the model group, the triglyceride content of medium in pioglitazone group and in the high dose of TNK decreased significantly (P<0.05).Under the stimulation of high fat, the expression of NF-KB mRNA and protein in the hepatocyte increased significantly, the expression of PPAR-a mRNA and p-AMPK protein were inhibited, the phosphorylation level of JNK protein increased and the expression of p-IRSl protein decreased. With the intervention of TNK, the expression of NF-KB mRNA and protein in the hepatocyte decreased significantly, the expression of PPAR-a mRNA and p-AMPK protein increased, the phosphorylation level of JNK protein decreased and the expression of p-IRSl protein increased.Conclusions:1. TNK could reduce2-hour postprandial blood glucose of IGT patients, which is significant in clinical effect.2. TNK can improve the disorder of glucose and lipid metabolic in liver under the high glucose environment, which may be associated with increasing insulin sensitivity of hepatic.3. TNK may relieve the disorder of lipid metabolism mediated by inflammation via inhibiting the elevation of NF-kb induced by high fat, activating the gene transcription of PPAR-a, down-regulating the phosphorylation of JNK and up-regulating the phosphorylation of IRSl, which is one of the mechanisms of improving the disorder of glucose and lipid metabolic in hepatocyte.