| Type 2 diabetes mellitus(T2DM), a kind of metabolic diseases, is associated with chronic high blood glucose, and can cause many complications, including eyes, feet, kidneys, nerves, heart and blood vessels. In the past few decades, rapid increases in the rate of T2 DM and its high fatality rate had become a serious problem worldwide. Lactic acid bacteria(LAB) and its exopolysaccharides(EPS) are safe, reliable and healthy materials with less side effects, so its beneficial effect has been widely recognized in clinical application and experimental research. As a kind of dietary supplementation, lactic acid bacteria have favorable effects in the intestinal tract. Recenty, the association between gut flora and diabetes had become a newly-emerging hot spot and enormous researchers had focused on this filed. Thus, we investigated the effects of exopolysaccharide-producing lactic acid bacteria on T2 DM through gut microbiota related insulin resistance pathway, and then NCI-H716 cell model was used to evaluate the hypoglycemic mechanism and its influencing factors.At first, the yield of exopolysaccharide was determined with phenol sulfuric acid method. According to the EPS-producing abilities, probiotics were divided into high, middle and low EPS-producing groups. ?-glucosidase inhibitors regulated blood glucose balance by slowing the digestion of carbohydrates in the intestines. In vitro, both high and middle EPS-producing LAB had the better ability to inhibit ?-glucosidase activity. The effect of LAB with different EPS-producing on high-fat and low-dose streptozotocin(STZ)-induced type 2 diabetes in mice was studied. These results showed that middle EPS-producing LAB favorably regulated blood glucose level, glucose tolerance, glycosylated hemoglobin, leptin, and inflammatory cytokines in the diabetic mice.The anti-diabetic effects of live and dead multi-strain probiotics were explored and compared in a high-fat and streptozotocin-induced model of type 2 diabetes in mice. Data indicated that both live and dead multi-strain probiotics reduced blood glucose levels, improved glucose tolerance, and protected against the impairment of the pancreas, while the live probiotic showed a greater ability to increase the abundance of Lactobacillus, Akkermansia and Bifidobacterium in the intestines, and enhance butyrate production, and regulate inflammatory response and then ameliorate insulin resistance.To explore the better strain with hypoglycemic ability, five middle EPS producing LAB were respectively fed to the diabetic mice. The results showed that the hypoglycemic ability of L. casei CCFM419 and L. plantarum X1 were better than other bacteria. The two probiotics exerted the beneficial effect of ameliorating insulin resistance through insulin resistance pathway. In addition, they also stimulated insulin secretion, enhanced antioxidant capacity, and regulated serum lipid metabolism. Compared with L. plantarum X1, L. casei CCFM419 feeding mice showed a higher abundance in butyrate-producing bacteria Allobaculum, as well as a stronger antioxidant capacity and protective effect on pancreatic islets. Therefore, L. casei CCFM419 could be as a potential probiotics to ameliorate diabetes.The dose-effect relationship between L. casei CCFM419 and hypoglycemic effect was investigated in mice with type 2 diabetes. The results demonstrated that all concentrations of L. casei CCFM419 could partly alleviate diabetes. Especially, at the concentration of 5 × 10~9 CFU, it has the greatest beneficial effects with a higher abundant butyrate-producing bacteria Allobaculum, improving systemic inflammatory response, lipid profiles, and antioxidant defenses.The mRNA change in mice intestine showeded that 5 × 10~9 CFU L. casei CCFM419 significantly up-regulated proglucagon GCG and Prohormone Convertase PC3 mRNA, and then obviously increased GLP-1 secretion in mice intestine. Thus, we hypothesis that L. casei CCFM419 exerted its hypoglycemic effects through enhancing GCG and PC3 mRNA levels, and then stimulating GLP-1 secretion in L cells. On this basis, the effect of L. casei CCFM419 on GLP-1 secretion. Consistent with the results of animal experiments, NCI-H716 cells treated with 5 × 10~9 CFU L. casei CCFM419 exhibited the similar results. In addition, NCI-H716 cells were also stimulated by exopolysaccharide purified from L. casei CCFM419 and butyrate, and then both factors increased GLP-1 secretion. These results suggested that L cells may be one of the hypoglycemic target cells of lactic acid bacteria in the intestinal tract, and exopolysaccharide and butyrate were the related factors on ameliorating diabetes. |
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