Study On The Effect And Mechanism Of Wheat Grem Peptide On Alleviating Type ? Diabetes

Type ?diabetes mellitus is a complex metabolic disease characterized by insulin resistance.The drugs for the treatment of type ? diabetes are usually accompanied by severe side effect.Therefore,the development of natural hypoglycemic active substances without side effects have been receiving growing attention.Wheat germ are rich protein and a variety of bioactive substances,which is known as "human natural nutrition treasure house".However,the utilization rate of wheat germ is low,and it is often discarded as feed or by-product during the wheat processing.In order to promote the further processing and utilization of wheat germ,this study aimed to study the bioactivities of the 6-10 amino acid peptide extracted from wheat germ protein by enzymatic hydrolysis.For example,their activity of alleviating insulin resistance was evaluated using a vitro model of insulin resistance in Hep G2 cells,and we screened out the peptide sequence ADWGGPLPH,which possessed the strongest activity in alleviating insulin resistance.Then,the mechanism of the peptide ADWGGPLPH in improving type ? diabetes mellitus was investigated.The main research contents and results were as follows:(1)An in vitro model of insulin-induced insulin resistance in Hep G2 cells was used to evaluate the anti-diabetic activity of the wheat germ active peptide ADWGGPLPH in the cellular level.The results showed that ADWGGPLPH significantly increased the glucose consumption and glycogen content in Hep G2 cells,with increase in the activities of hexokinase(HK)and pyruvate kinase(PK).(2)A popular type ? diabetes rat model induced by a high-fat diet combined with streptozotocin injection was used to investigate the anti-diabetic activity of the peptide in the animal level.The results showed that ADWGGPLPH alleviated the symptoms of lower weight gain and polydipsia,significantly reduced the fasting blood glucose content and insulin resistance index of rats,alleviated the insulin resistance of rats,improved the lipid deposition in blood and increased the liver glycogen content of rats.Moreover,type ? diabetes-associated liver swelling and abnormal tissue structure was also improved by the peptide supplementation.(3)The expression of SOCS3 / IRS1 / AKT in rat liver and Hep G2 cells was detected.The results showed that ADWGGPLPH significantly reduced the expression of SOCS3,inhibited the phosphorylation of IRS1 serine 307 sites,and then activated the phosphorylation of AKT,thus promoting the transmission of insulin signaling pathway and enhancing insulin sensitivity,with relieved insulin resistance.ADWGGPLPH also promoted the phosphorylation of GSK 3?,reduced the expression of FOXO1,and increased the expression of GLUT2,thus promoting glycogen synthesis,reducing gluconeogenesis,increasing tissue glucose transport,and improving the abnormal glucose metabolism caused by insulin resistance.(4)Lipid metabolism-related proteins in rat liver were detected.The results showed that ADWGGPLPH upregulated the expression of nuclear factor PPAR?,downregulated the expression of downstream sterol regulatory element SREBP1,improved the expression of downstream ACC and FAS,inhibited the excessive synthesis of fatty acids,promoted the oxidation of fatty acids,and then improved the abnormal liver lipid metabolism caused by type ? diabetes.In conclusion,ADWGGPLPH could promote insulin signaling through SOCS3 /IRS1 / AKT signaling pathway,thus promoting glucose metabolism and improving type ? diabetes mellitus,with improvement of lipid metabolism in type ? diabetic rats.