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Effects Of Different Polysaccharides On Type 2 Diabetes And Anti-diabetic Mechanism Of Arabinoxylan

Posted on:2021-04-27Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q X NieFull Text:PDF
GTID:1361330602478286Subject:Food Science and Engineering
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Type 2 diabetes(T2D)is one of the major health problems that carries a great economic and living burden to people,which strongly influences the quality of humans’ life.Polysaccharides is an abundant natural macromolecular.A number of studies reported that polysaccharides have hypoglycemic effect,whereas the difference among different polysaccharides on T2D is still not clear.Arabinoxylan from the seeds of Plantago asiatica L.is characterized by high viscosity and rich in xylose(60%)and arabinose(32%).It was found that the arabinoxylan had a notable influence on slowing down glucose diffusion in vitro;along with significantly reduced serum total triglyceride,atherogenic index and improved the structure of colon microbiota in vivo.The present study was to evaluate the effects of different polysaccharides on T2D.We further investigated the anti-diabetic mechanism of arabinoxylan.The main contents and results are as follows:(1)The effects of different polysaccharides(guar gum,carrageenan,apple pectin,xylan,arabinogalactan,xanthan gum,glucomannan,β-glucan and arabinoxylan)on T2D were compared by high-fat diet and low dose streptozotocin-induced type 2 diabetic rats.The results indicated that not all polysaccharides have hypoglycemic effects.Administration of β-glucan,arabinogalactan,guar gum,apple pectin,glucomannan and arabinoxylan significantly reduced the fasting blood glucose,whereas carrageenan,xylan and xanthan gum had no effect on glycemic control in type 2 diabetic rats.Polysaccharides with hypoglycemic effects increased the level of butyric acid and abundance of some beneficial bacteria(Anaeroplasma,Parabacteroides and some butyric acid-producing bacteria),as well as improved host metabolism by decreasing concentrations of 12α-hydroxylated bile acids,acylcarnitines,and some amino acids(leucine,phenylalanine,citrulline,glutamate,and etc.)in type 2 diabetic rats.It was also found that only β-glucan can attenuate T2D via improvement of Prevotella copri-mediated branched chain amino acid(BCAA)metabolism.(2)The effects of arabinoxylan on physiological status of type 2 diabetic rats were studied.Administration of arabinoxylan caused significant decreases in the concentrations of fasting blood glucose,serum insulin,total cholesterol,triglyceride,non-esterified fatty acid and maleic dialdehyde,and significant increases in the levels of high-density lipoprotein cholesterol and the activities of antioxidant enzymes(CAT,SOD and T-AOC)compared with diabetic rats after 4 weeks’ treatment.Type 2 diabetic rats showed significant renal impairment,including glomerular hypertrophy with mesangial matrix expansion,interstitial fibrosis,and tubular atrophy,as well as the significantly increased serum creatinine,uric acid,and urea.Supplementation with arabinoxylan partially improved renal impairment in type 2 diabetic rats.Furthermore,the concentrations of short-chain fatty acids(SCFAs)were significantly decreased in feces of diabetic rats,arabinoxylan treatment could increase SCFAs in rats of T2D.(3)The effects of arabinoxylan on host metabolism in type 2 diabetic rats were studied.UPLC-Triple-TOF/MS-based serum metabolomic and lipidomic analysis indicated the significantly changed host metabolism in type 2 diabetic rats.Metabolomics analysis revealed that BCAAs,12α-hydroxylated bile acids,ketone bodies,and several short-and long-chain acylcarnitines were significantly increased in diabetic rats,whereas lysophosphatidylcholines(LPCs)were significantly decreased.Lipidomics analysis indicated T2D-related dyslipidemia was mainly associated with the increased levels of acetylcarnitines,free fatty acids(FFA),diacylglycerols,triacylglycerols,and cholesteryl esters and the decreased levels of some unsaturated phosphatidylcholines(less than 22 carbons).These changed metabolites were mainly involved in amino acid,carnitine and bile acid metabolism,which suggested the accumulation of incompletely oxidized lipid species in T2D might eventually contribute to impaired insulin action and glucose homeostasis.Arabinoxylan treatment decreased the concentrations of 12α-hydroxylated bile acids,carnitines and FFAs,as well as increased the levels of LPCs.The improved bile acid and lipid metabolism by arabinoxylan might be involved in the alleviation of hypercholesterolemia and hyperlipidemia in T2D.(4)The effects of arabinoxylan on urine metabolomic profile of type 2 diabetic rats were studied.T2D caused a significant increase in the levels of acetone,glucose,2-oxoglutarate and leucine,and a significant decrease in the concentrations of creatine,histidine,lysine,1-tryptophan,hippurate,L-cysteine,kynurenine,and arabitol as compared with normal rats.These 12 metabolites(with VIP cut-off value>1)can be used as biomarkers in T2D.A total of 21 urinary metabolites are significantly improved by arabinoxylan treatment.These metabolites mainly belong to amino acids and organic acids,and which are mainly involved in TCA cycle,and metabolism of lipid and ketone body,taurine and hypotaurine,tryptophan,and BCAAs.Arabinoxylan administration could improve carbohydrate,lipid,and amino acid metabolism in T2D.(5)The effects of arabinoxylan on gut microbiota of type 2 diabetic rats were studied.Based on 16S rRNA gene high-throughput sequencing,there was no significant difference on α-diversity index between normal and diabetic rats,whereas low-dose arabinoxylan supplementation significantly increased α-diversity in type 2 diabetic rats.T2D-induced significant increase in Actinobacteria,Bacteroidetes,Proteobacteria,and a significant decrease in Firmicutes at the phylum level.T2D also increased the abundance of Escherichia-Shigella,Bifidobacterium,Klebsiella,Lactobacillus,Parasutterella,Turicibacter,Desulfovibrio,and decreased abundance of Lachnoclostridium,Lachnospiraceae NK4A136 and Lachnospiraceae UCG-001 at the genus level.Arabinoxylan intervention reduced the abundance of Bifidobacterium,Escherichia-Shigella,Klebsiella,Lactobacillus,Parasutterella,Desulfovibrio,and increased the abundance of Lachnospiraceae UCG-001.Supplementation with arabinoxylan can alleviate the T2D-induced gut microbiota dysbiosis.In conclusion,we found not all polysaccharides alleviate T2D,and the hypoglycemic effects of polysaccharides mainly relies on the modification of gut microbiota and the production of butyric acid.Arabinoxylan can alleviate T2D via the improvement of carbohydrate,lipid and amino acid metabolism.
Keywords/Search Tags:type 2 diabetes, polysaccharides, arabinoxylan, gut microbiota, metabolomics, short chain fatty acids
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