| In recent years,the number of diabetic patients is increasing.According to the International Diabetes Federation,the number of the population with diabetes is predicted to increase to 629 million in 2045.Despite the application of some drugs in the treatment of diabetes,the drugs easily trigger a few serious side effects and damage the quality of life.So it is essential to develop the hypoglycemic drugs used as effective treatments for diabetes.More attentions are paid on lactic acid bacteria(LAB)due to their lesser side effects,free availability and safety.Recently,although many researchers have confirmed the hypoglycemic activity of LAB or foods fermented with LAB,the molecular mechanism remains to be elucidated.Thus,further research on the hypoglycemic mechanism of LAB is needed.?-Glucosidase inhibitory activities of eight L.paracasei strains isolated from Tibet Autonomous Region in China previously were assessed in vitro according to the method of p-nitrophenyl-?-D-galactopyranoside(PNPG).And L.paracasei TD062 with high ?-glucosidase inhibitory activity showed the excellent antidiabetic ability.Then the tolerance of L.paracasei TD062 to acid,bile salts and gastrointestinal juices was evaluated.Moreover,based on an animal model of diabetes,the beneficial effect of the strain was investigated.Furthermore,the underlying hypoglycemic mechanism of L.paracasei TD062 was explored by real-time RT-PCR.We obtained the results as followed in the study:1.?-Glucosidase inhibitory activities of eight L.paracasei strains were determined by the method of PNPG.The results showed that these strains exhibited different inhibitory activities against ?-glucosidase.And the highest inhibitory activity was found in L.paracasei TD062(31.89%),exhibiting the excellent antidiabetic effects.Therefore,L.paracasei TD062 was selected to investigate the hypoglycemic effects in diabetic mice.2.The survival rate of L.paracasei TD062 was 91.08% after exposure to acidified conditions for 3 h with the value of 7.45 log cfu/mL.Then exposed to broth containing 0.3% bile salts for 4 h,the viable count was 6.99 log cfu/mL with survival rate as high as 85.45%.And the viable count was reduced to 7.36 log cfu/mL with the survival rate of 89.98%.Moreover,total viable count was reduced to 6.54 log cfu/mL after the strain was incubated in simulated intestinal juice with the survival rate of 79.95% and the viable counts of the strain decreased by 2 log units.These results implicated that L.paracasei TD062 was resistant to the acid,bile salts and gastrointestinal tract.3.The diabetic mice induced by high-glucose-fat diets and low-dose streptozotocin were treated with the strain to investigate the hypoglycemic effects in vivo.The results showed that administration of L.paracasei TD062 could decrease the levels of fasting blood glucose,postprandial blood glucose,glycosylated hemoglobin and insulin,inhibit weight loss and improve glucose tolerance.In addition,the dyslipidemia,oxidative stress and inflammatory reaction were also ameliorated by oral administration of L.paracasei TD062.4.To evaluate the expression levels of genes related to glucose metabolism and signaling pathways,total RNA were extracted from liver tissues.And the RNA expression levels of genes were determined by real-time RT-PCR system.It could be seen that the expression of PEPCK,G-6-Pase and GSK-3? were significantly upregulated in comparison with the diabetes mellitus group(P<0.05).In contrast,downregulation of IRS-2,PI3 K and Akt expression were obtained in diabetic groups and the effects were dose-dependent to some extent.Here,we concluded that regulatory mechanism of L.paracasei TD062 may be to ameliorate insulin resistance,elevate the insulin sensitivity of peripheral tissues and regulate the glucose levels by activating insulin signaling pathway. |
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