| Diabetes mellitus is a common endocrinic and metabolic disease characterized by hyperglycemia,with disorders of protein and fat metabolism as the main clinical manifestations.The disease is caused by absolute or relative insufficiency of insulin secreted by pancreatic islet ? cells in body.Diabetes is the world third most important non-communicable disease after tumors and cardiovascular diseases.In recent years,diabetes has become worsen in China,due to the rapid development of domestic economy,aging population,environmental pollution,unhealthy lifestyle,and mental stress.It not only causes serious harm to the patient's life quality,but also imposes a huge burden on medical system and economic development.Therefore,it is of massive importance to find effective methods for the prevention and treatment of diabetes.Cyclocarya paliurus(Batal.)Iljinskaja(C.paliurus)has been used as a substitute of tea over a thousand year,and its medicinal value has been gradually recognized.It is a kind of precious plant with great research value due to hypoglycemic,hypolipidemic,anti-aging bioactivities,etc.Polysaccharides are natural macromolecular substances with various biological functions.The benefits of polysaccharides to human health have been supported by a large number of research results.At present,the systemic research and mechanism discussion on the improvement of diabetes mellitus by polysaccharides of C.paliurus(CP)are still limited.In the current study,CP was used to investigate the effects on hyperglycemia,hyperlipidemia,the intestinal microbiota and metabolic dysfunction in type 2 diabetic rats,induced by streptozotocin(STZ)combined with a high-sugar and high-fat diet.The main research content and results are summarized as follows:(1)The effects of CP on glucose and lipid metabolism.Diabetic rats were randomly divided into 5 groups,and were orally given saline,metformin(70 mg/kg BW)and low(200 mg/kg BW),medium(300 mg/kg BW),high(400 mg/kg BW)doses of CP;normal rats were randomly divided into two groups,and were orally given CP(300 mg/kg BW)and saline,respectively.The gavage period continued for 3 weeks.Blood glucose,water consumption and body weight of rats were measured weekly.After 3 weeks of oral administration,the effects of CP on oral glucose tolerance,serum insulin,and lipid levels in type 2 diabetic rats were determined.The results showed that CP could significantly relieve the symptoms of type 2 diabetes,inhibit the weight loss of rats and relieve the symptoms of polydipsia and polyphagia;effectively reduce blood glucose level,increase blood glucose tolerance,and regulate insulin level in type 2 diabetic rats;effectively reduce the levels of total cholesterol(TC),triglyceride(TG),and low density lipoprotein(LDL-c)in the serum of diabetic rats and increase the level of high density lipoprotein(HDL-c)in serum of type 2 diabetic rats.CP improved the insulin resistance of type 2 diabetic rats by regulating the metabolism of blood lipids.(2)Further study the effects of CP on type 2 diabetes-induced pancreatic injury,liver damage,liver function abnormalities,hormone secretion and inflammatory response imbalance.Liver function test and histology test were used to reveal the protective effects of CP on the liver and pancreas;serum hormones and inflammatory factor were analyzed to exam the effect of CP on hormone secretion and inflammatory response in type 2 diabetic rats.The results indicated that CP significantly relieved the progression of type 2 diabetes from multiple directions and pathways: CP significantly reduced the pathological damage of pancreas,and improved the function of ? cells by regulating the Bax and Bcl-2 proteins expression of pancreatic tissue;effectively improved liver pathological damage and liver function,increased the bioactivities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and catalase(CAT)in the liver,and lowered the content of malonaldehyde(MDA)in liver,resulting improved function of ? cell and insulin resistance;effectively reduced the levels of serum inflammatory cytokines IL-1?,IL-6 and tumor necrosis factor-?(TNF-?)to ameliorate inflammatory status in type 2 diabetic rats,which in turn improved insulin resistance and promoted insulin secretion;regulated hormone levels including leptin(LEP),adiponectin(ADP),and glucagon-like peptide-1(GLP-1),which help to increase insulin sensitivity.In addition,CP also regulated the content of free fatty acid(FFA)in serum to achieve hypoglycemic function by restoring normal ?-cell function.CP could improve insulin resistance by improving pancreatic damage,liver damage,abnormal liver function,and regulating hormone secretion and inflammatory response levels.(3)In-depth study the effects of CP on gut microbiota and metabolic disorders in type 2 diabetic rats.Denaturing gradient gel electrophoresis(DGGE)and gas chromatography were used to analyze microbiota and their metabolites.The results suggested that CP could improve the structure of intestinal microbiota,promote the proliferation of beneficial bacteria such as Faecalibacterium prausnitzii,Prevotella,Clostridium,Ruminococcus,inhibit the growth of potential pathogens such as Lachnospira and Helicobacter,and improve the intestinal metabolic environment by improving the intestinal microbiota structure.Meanwhile,CP treatment increased intestinal production of short chain fatty acids(SCFAs),while also reduced intestinal p H and moisture content.These results indicated that CP improved the structure of gut microbiota in diabetic individuals,further changing the metabolic environment of the intestine.(4)Based on the results of this study,explore the mechanisms of the hyperglycemic effects of CP: CP firstly enriched beneficial bacteria and inhibited the proliferation of potential bacteria in the intestine through nutrient action,thereby changing the structure of the intestinal bacteria.Structural shifts of the intestinal bacteria resulted in changes of metabolic environment in intestine and then affected the immune response,hormone secretion,oxidative stress,the regeneration of pancreatic ?-cell and organ function and normalized the levels of above organism function to ameliorate the hyperglycemia and insulin resistance,which played a role in slowing down the progression of type 2 diabetes. |
PDF Full Text Request