Study On The Antidiabetic Effect Of Probiotics And Its Mechanisms

Diabetes is recognized as the world’s third largest fatal disease. The incidence ofdiabetes and the number of patients with diabetes around the world shows an increasing trendyear by year. And the proportion of patients with typeⅡdiabetes was more than90%. The useof medicines in diabetes has serious side effects such as diarrhea, drug resistance, andsecondary failure. In recent years, lactic acid bacteria (LAB) have become hot topic indiabetes prevention due to its natural property and security. Many studies have confirmed theusefulness of LAB in the prevention and therapy of diabetes, but the specific mechanismremains poorly elucidated. Therefore, the present study aimed to screen the potentialantidiabetic LAB, and their beneficial effects for diabetes were evaluated in vivo. In addition,the mechanism behind their antidiabetic properties was studied in cell models, and theirapplication value in practical production was finally considered.17LAB strains were screened for potential new probiotics using in vitro methods,including acid and bile salt tolerance, adhesion, antioxidative and-glucosidase inhibitoryactivity. LGG (Lactobacillus rhamnosus GG, ATCC53103) was used as a positive controlstrain in the present study. The results indicated that CCFM0412(L. casei CCFM0412) andCCFM0528(L. rhamnosus CCFM0528) showed better potential probiotics properties and-glucosidase inhibitory activity in vitro, whereas CCFM11(L. plantarum CCFM11) showedthe worst potential probiotics properties. A principal component analysis (PCA) showed thatthe characteristics of CCFM0412were better than those of LGG, and CCFM0528was themost similar strain to LGG. However, the score of CCFM11was the lowest.A mice model of typeⅡ diabetic induced by a high-fat diet and streptozotocin (STZ)injection was used for evaluating preventive and therapeutic effects of CCFM0412,CCFM0528and CCFM11. The results showed that CCFM0412and CCFM0528significantlydecreased fasting and postprandial2-h blood glucose, and exerted better preventive effects ondibetes when compared with LGG. However, the level of blood glucose in CCFM11groupwas higher than that of the CCFM0412and CCFM0528-treated groups. Furthermore,CCFM0412and CCFM0528decreased the values of glycosylated hemoglobin (HbA1c),endotoxin, proinflammatory cytokines and blood lipid, and increased the levels of insulin andglycogen. Additionally, these two strains significantly improved oxidation indicators andprotected the islets of Langerhans. In general, the antidiabetic effects of CCFM0412andCCFM0528in prevention groups was better than in the therapeutic groups, even someindicators were better than in the LGG group.The mechanism behind the antidiabetic effects of LAB was evaluated by cell models andanimal experiments. The results indicated that CCFM0412and CCFM0528decreased theexpressions of sucrase-isomaltase (S-I), sodium glucose cotrans poners l (SGLT-l), andfacilitative glucose transporters2(GLUT-2) mRNAs of the intestinal mucosa in diabeticmice. The effects of CCFM0412and CCFM0528in inhibitingthe-glucosidase activity andglucose absorption, and regulating the expressions of S-I, SGLT-l, and GLUT-2mRNAswere verified in the Caco-2monolayer transwell models. CCFM0412and CCFM0528 regulated the expressions of cytokines mRNAs in the spleens of mice,, decreased theexpressions of pro-inflammatory cytokines mRNAs and increased the expression ofanti-inflammatory cytokines mRNAs; and their regulatory roles were better than CCFM11.Moreover, the effects of LAB on regulating the cytokine secretion and the expressions ofcytokines mRNAs were verified in an inflammatory model of HT-29cells. LAB increasedthe expressions of translocation of glucose transporter4(GLUT-4), peroxisomeproliferator-activated receptor (PPAR-), and peroxisome proliferator-activated receptor γ(PPAR-γ) mRNAs in the lives of diabetic mice, decreased the blood glucose and lipid, andimproved the insulin resistance (IR). The effects of LAB on improving the IR and regulatingthe expressions of GLUT-4, PPAR-γ and PPAR-mRNAs were demonstrated in IR model ofHepG2cells.In the study of dairy and soy products application of CCFM0412and CCFM0528, thesetwo strains could be applied in fermented milk production as supplementary culture whichwas not detrimental either to other strains in fermented milk or the chemical and physicalindicators. CCFM0412and CCFM0528had a pretty good growth and acid productionabilities in soybean milk which made them suitable as a starter culture for sour soya-beanmilk production. Therefore, CCFM0412and CCFM0528could be used to developcommercially functional fermented products.