Summary of new aspect of the thesis: Nghiên cứu độc tính và tác dụng hạ glucose máu của viên Andiabet trên thực nghiệm

Several new models have been implemented: evaluate the effect inhbitivity on hyperglycemic postprandial blood glucose of reagent in glucose/sucrose/starch tolerance test in normal and diabetic mice and the effect antagonism with insulin resistance in type 2 diabetic mice (the technique of "Hyperinsulinemic - euglycemic clamp test")
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Summary of new aspect of the thesis: Nghiên cứu độc tính và tác dụng hạ glucose máu của viên Andiabet trên thực nghiệm 1 INTRODUCTION Type 2 diabetes mellitus (T2D) is a metabolic disorder withcomplex mechanisms and pathophysiological abnormalities. It isextremely hard to reverse T2D disease state with monotherapy. Thuscombination therapy is becoming a promising alternative choice inclinical practice by designing drug combinations or compound drugsto interact with multiple targets and achive synergitic treatment effect.For example, traditional Vietnamese medicines are attracting moreattentions for their efficacy and less frequent side effects for treatingT2D. Lagerstroemia speciosa (L.) Pers; Gynostemma pentaphyllum(Thunb.) Makino; Anemarrhenae Aspheloides (Bunge) has beenreported to alleviate hyperglycemia and hyperlipemia in manypreclinical and clinical studies and have been combined into the softform of Vinabetes. However, Vinabetes has only been extracted inlaboratory and there are no adequate pharmacological studies.Andiabet is a compound of 3 Vietnamese herbal medicinescomposition above. The aim of this study was to investigate thetoxicity and the hypoglycemic effect of Andiabet in experimentalanimals with the following objectives:1. Determine of acute toxicity and longterm toxicity by Andiabet.2. Evaluate the hypoglycemic effect and several hypoglycemicmechanisms of Andiabet tablets in experiment. Chapter 1. OVERVIEW1.1. OVERVIEW ABOUT THE DIABETES MELLITUS1.1.1. Definition, classification, diagnostic criteria for diabetes andpathogenetic mechanism of diabetes type 21.1.1.1. Definition “Diabetes is a metabolic disorder characterized byhyperglycemia, the result of a deficiency of insulin secretion; impairedfunctioning of insulin; or both. Chronic hyperglycemia is often 2associated with damage, disorders and impaired function of many organs, especially the eyes, kidneys, nerves, heart and blood vessels.”1.1.1.2. Classification: Diabetes is divided into 4 types: diabetes type1, type 2, diabetes pregnancy and special types. In which, type 1 andtype 2 diabetes is most common.1.1.1.3. Diagnostic criteria for diabetes Four diagnostic tests for diabetes are currently recommended,including measurement of fasting plasma glucose; 2-hour (2-h) post-load plasma glucose after a 75 g oral glucose tolerance test (OGTT);HbA1c; and a random blood glucose in the presence of signs andsymptoms of diabetes. People with fasting plasma glucose values of ≥7.0 mmol/L (126 mg/dl), 2-h post-load plasma glucose ≥ 11.1 mmol/L(200 mg/dl), HbA1c ≥ 6.5% (48 mmol/mol); or a random bloodglucose ≥ 11.1 mmol/L (200 mg/dl) in the presence of signs andsymptoms are considered to have diabetes1.1.1.4. Pathogenetic mechanism of diabetes type 2 Insulin resistance in peripheral tissues and insulin secretiondisorders are two important and related closely factors in thepathogenesis of type 2 diabetes, which usually occurs before theclinical manifestations of diabetes (from the pre-diabetes phase).However, in patients with type 2 diabetes who are not overweight, themanifestation of insulin secretion is the opposite, whereas in type 2diabetes patients with obesity, insulin resistance is the main condition.Genetic and environmental factors play a role in promoting diseasedevelopment and development.1.2. GROUPS OF MEDICINE TREATMENT FOR DIABETESCurrently, in addition to lifestyle adjustment (diet and exercise), drugsshould be used to treat of type 2 diabetes. The drugs for treatment oftype 2 diabetes focus on the following main groups:1.2.1. Drugs stimulate insulin secretion include: KATP channel 3inhibitors are: sulfonylurea and meglitinide. The incretin modulatorsare: GLP-1 analogues: Exenatid, Liraglutid, Lixisenatid and DPP-4inhibitors: sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin.1.2.2. Drugs reduce insulin resistance include: metformin andthiazolidinedion: pioglitazon1.2.3. Drugs reduce/slow absorption of glucid: drugs a-glucosidaseinhibitors include: acarbose (Precose, Glucobay) and miglitol (Glyset).1.2.4. Drugs increase renal glucose excretion: SGLT2 inhibitors are:Dapagliflozin, Canagliflozin and Empagliflozin1.3. SEVERAL DIABETIC RESEARCH METHODS INEXPERIMENTANT1.3.1. The invivo research model.1.3.1.1. Models of type 1 diabetes: Spontaneous type 1 diabetes (T1D)models and secondary T1D models induced by chemicals, removingpancreas or virus.1.3.1.2. Models of type 2 diabetes: Obese and non-obese spontaneousT2D rodents models. Secondary T2D models: induced by chemicalsor a high-fat diet combined with low-dose STZ and by geneticmodification.1.3.1.3. Several methods to evaluate hypoglycemic effect in invivo:Assessing the ability of the drug on glucose tolerance test,polysaccharide absorption. Assessing the drug’s effect of increasinginsulin sensitivity to the target tissue via the techniqueHyperinsulinemic - euglycemic clamp test1.3.2. The invitro research model. The invitro research model can be divided into two categories:assessing the of drug’s effect on organs, isolated cells and on enzymesinvolved glucose homeostasis.1.4. OVERVIEW COMPONENTS OF ANDIABET ANDRESEARCHS RELATED TO ANDIABET 4 Lagerstroemia speciosa (L.) Pers; Gynostemma pentaphyllum(Thunb.)Makino; Anemarrhenae aspheloides (Bunge) was estimatedfor hypoglycemic virtue in many preclinical and clinical studies andhave been combined into the soft form of Vinabetes. Vinabetes with a1,5:1,5:1 weight ratio of the three herbal composition, similar toAndiabet was performed acute toxicity test and LD50 dose was 42.98g/kg mice. Vinabetes has also been studied for long term toxicity test inrabbits for ...