| Type 2 diabetes(T2DM)is a chronic metabolic disease that involves systemic glucose metabolism,lipid metabolism,and amino acid metabolic disorders and its pathogenesis is complex.Type 2 diabetes is accompanied by serious complications with high mortality rate.It is the third most serious non-communicable chronic disease that threatens human health after cancer and cardiovascular and cerebrovascular diseases.Resistant starch is a kind of starch that has anti-enzymatic properties because of its special structure.It is not digested and absorbed in the small intestine,but it can be digested and utilized by the micro-organisms in the colon in the colon,which in turn exerts beneficial physiological effects.One of the new dietary fibers.A number of studies reported that resistant starch(RS)can improve insulin sensitivity and reduce fasting blood glucose in humans and animals,but little is known about its therapeutic mechanism.At the same time,as the most widely used drug for the treatment of T2DM—metformin,its exact mechanism for improving T2DM remains controversial.Based on UPLC-Q-TOF-MS non-targeted serum metabolomics and intestinal microbiota diversity,this study systematically studied T2DM with resistant starch,and conducted a comprehensive comparative study with first-line hypoglycemic agent metformin.1 Study on the effect of resistant starch on blood glucose in T2DM rats First of all,this study used high-fat high-sugar diet+low-dose STZ to induce T2DM rat model.After 11 weeks of continuous administration,the efficacy of resistant starch in type 2 diabetic rats was observed and compared with the therapeutic effect of metformin.The results showed that resistant starch could produce Metformin-like effects,which can significantly reduce fasting blood glucose,improve glucose tolerance,and relieve pathological damage caused by T2DM in rats.Also,we also found that resistant starch maintains body mass and improves blood lipid disorders are better than metformin.2 Based non-targeted serum UPLC-Q-TOF-MS metabolomics study The first part of this experiment found that resistant starch T2DM treatment can produce Metformin-like effects,but the underlying mechanism is unclear.After 11 weeks of dosing,UPLC-Q-TOF-MS method was used to perform non-targeted analysis on serum of normal group,model group,metformin-treated group,and resistant starch-treated group,combined with the multiplicity of PCA and OPLS-DA to identify potential biomarkers.Databases such as KEGG are used to elucidate the biological significance of metabolites and to find links between potential biomarkers.From the perspective of metabonomics to determine the role of resistant starch to improve the mechanism of T2DM,at the same time compared the similarities and differences in the mechanism of action of metformin with the first-line use of type 2 diabetes,systematically explain its mechanism of treatment of T2DM.The results indicate that regulated disordered glycerophospholipid metabolism,sphingomyelin metabolism,linoleic acid metabolism,valine,leucine and isoleucine metabolism,phenylalanine and tyrosine metabolism,and tryptophan metabolism pathway may be the common mechanism of them in T2DM treatment,and the role of resistant starch in the treatment of T2DM may also be related to the correction of disorder bile acid metabolic pathways.3 Based on the microbial diversity of 16s-rRNA gut microbiota study The second part of this project uses metabonomics to find that resistant starch and metformin have similar therapeutic mechanisms for type 2 diabetes.Resistant starch,due to its particular structure,remains intact before reaching the colon where could be used by the gut microbiota.The use of fermentation ultimately modulates the composition and metabolites of the gut microbiota and exerts beneficial physiological effects.Therefore,the gut microbiota is considered to be a key factor affecting the metabolic health of resistant starch.With the deepening understanding of the gut microbiota more and more evidence shows that the gut microbiota may also be the target organ for the metformin hypoglycemic effect.Metformin may also exert its efficacy by adjusting the disturbance of gut microbiota caused by T2DM.Therefore,the comparison of gut microbes and related intestinal metabolites mediated by resistance and metformin will help to understand the role of gut microbes in the treatment of type 2 diabetes and the similarities and differences between resistant starch and metformin in the treatment of T2DM.And deepen understanding of the intestinal tract in the treatment of T2DM.The results showed that the resistant starch and metformin had similar improvements in the microbiota,but metformin was less effective than the resistant starch in controlling the flora(change in microbiota diversity).Using the Lefse analysis method,it was found that although there are specific differences in the genus level,the two are significantly enriched in the genus of fatty acid bacteria.The results of determination of short-chain fatty acids also confirmed that both resistant starch and metformin increased the content of acetic acid and butyric acid in the intestine.Combined with the first part of the study of metabolomics mechanism,we speculated that the therapeutic effects of resistant starch and metformin on type 2 diabetes might be based on improving the abundance of SCFAs produced in the intestine,especially the content of butyric acid and acetate,and thus regulating lipids.Metabolism and amino acid metabolism.It is worth noting that the diversity of resistant starch and intestinal flora is higher than that of metformin,which may be related to better maintenance of body mass and improvement of lipid metabolism and bile acid metabolism in the resistant starch group compared with the metformin group.In conclusion,based on non-targeted metabolomics and gut microbiota research,combined with pharmacodynamics,pathological sections,and immunohistochemical data,all suggest that the resistant starch and metformin may have therapeutic effects on type 2 diabetes by modifying some specific bacterial populations.About change,the regulation of lipid metabolism and amino acid metabolism through the increase of short-chain fatty acids may be the common mechanism of action of both,and resistant starch is more dependent on this.This study revealed for the first time that resistant starch had metformin-like effects and mechanisms in the intervention of diabetes mellitus in T2DM rats,which provided a useful reference for the future use of resistant starch in the T2DM population for food and development as an auxiliary hypoglycemic functional health food. |
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