| Type 2 Diabetes Mellitus(T2DM)is a complex metabolic disorder characterized by hyperglycemia,insulin resistance and β-cell failure.Its occurrence is related to genetic,environmental and dietary factors,which can seriously affect the body’s glucose metabolism and cause great impact on physical health.Because taking hypoglycemic drugs is easy to produce nausea,flatulence,diarrhea and other adverse reactions,replacing hypoglycemic drugs with animal and plant extracts has become a new way to improve T2 DM,which is in line with the “food and nutrition approach” to solve the sub-health problem of Chinese people.Peptides had been widely concerned because of their wide sources,simple preparation and diverse activities.Studies had shown that pea peptides,rye peptides and quinoa peptides had hypoglycemic effects.Camel milk is a precious special milk with rich protein species and balanced amino acid composition,which is a good source for the preparation of food-derived active peptides.It had been proved that camel milk had good hypoglycemic effect.However,there are few studies on the isolation and preparation of hypoglycemic peptides from camel milk,and the mechanism against T2 DM of camel milk peptides(CMPs)is still unclear.Therefore,camel milk peptides were prepared from fresh camel milk to investigate their hypoglycemic effects in T2 DM mice,and the hypoglycemic mechanism of camel milk peptides was investigated using the structure of gut microbiota and gut microbiota metabolites as the entry point.The main research results are as follows:(1)The camel milk peptides were prepared referred to the previous preparation method of DPP-Ⅳ(Dipeptidyl peptidase-4)inhibitory peptides from camel milk in our laboratory.Camel milk protein was hydrolyzed by pepsin at 37℃ and p H 2.0 for 2 h,and then digested by trypsin at 37℃ and p H 8.0 for 4 h.The enzymatic digest was ultrafiltered and lyophilized to obtain camel milk peptides(<3 k Da),and their DPP-Ⅳ inhibition rate were 82.52±1.43%.830 camel milk peptide sequences were identified by LC-MS/MS technology,of which 34 peptides had potential DPP-Ⅳ inhibitory activity;(2)T2DM mice were intervened with 250 mg/kg and 500 mg/kg doses of camel milk peptides for 28 days to explore the effect of camel milk peptide on blood glucose regulation and tissue health status.The results showed that camel milk peptides decreased FBG and FINS,improved glucose tolerance and insulin tolerance,and alleviated the level of insulin resistance in T2 DM mice.Camel milk peptides increased ADP and oxidative stress level,decreased LEP,PYY,GLP-1,LPS and inflammatory factors level,improved lipid metabolism disorder and liver and kidney function in T2 DM mice.Camel milk peptides increased the size of atrophied islets and made them have regular shapes,reduced the size and number of fat particles in liver cells,protected the glomerulus from stiffness and decreased the size of white adipocytes;(3)Using 16 S r DNA high-throughput sequencing technology to explore the effect of camel milk peptides on gut microbiota of T2 DM mice.It was found that the intervention of camel milk peptides could improve the richness,diversity and uniformity of microbial species,reshape the structure of gut microbiota,and increase the content of total short-chain fatty acids,acetic acid,propionic acid and butyric acid in T2 DM mice.Camel milk peptides interfered with the relative abundance of Firmicutes to regulate the levels of GLP-1 and LPS and then interfere with blood glucose in T2 DM mice.Camel milk peptides could also interfere with T2 DM mice by affecting the relative abundance of Blautia and Allobaculum and affecting the level of short-chain fatty acids;(4)UHPLC-MS/MS metabolomics technology combined with multivariate statistical method was used to explore the effect of camel milk peptides on gut microbiota metabolites of T2 DM mice.A total of 84 differential metabolites were screened out from the feces of T2 DM mice,and it was found that camel milk peptides mainly affected organic acids and alcohols,etc.It was found that 3 metabolic pathways were highly correlated with gut microbiota metabolites,and camel milk peptides could regulate pantothenate and Co A biosynthesis pathways and increase pantothenic acid levels to improve T2 DM.In conclusion,camel milk peptides lowered blood glucose,changed the structure of type2 diabetes and regulated gut microbiota metabolites in T2 DM mice.This study revealed that camel milk peptides exerted its anti-T2 DM effect by regulating gut microbiota and its metabolites.The research results provided a theoretical basis for camel milk as an important source of food-derived hypoglycemic peptides,and provided new ideas for improving the added value of camel milk processed products. |
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