| Type 2 diabetes mellitus(T2DM)is a chronic disease mainly distinguished by hyperglucagonemia and insulin resistance.In recent years,the prevalence of T2DM is increasing annually.The commonly prescribed hypoglycemic drugs will have side effects in varying degree,which will both reduce the quality of life and aggravate the economic burden in patients.Therefore,it is urgent to find natural hypoglycemic substances with non-toxic side effects and explore its hypoglycemic mechanism.Studies have shown that gut microbiota disorder is closely related to the development of T2DM.Therefore,it is important to explore the role and mechanism of probiotics in the improvement of T2DM by targeting the gut microbiota.This study is aim to establish a mice model of T2DM through high-fat diet combined with intraperitoneal injection of streptozotocin,and further explore the antidiabetic effects of Lactobacillus rhamnosus LRa05(LRa05),Lactobacillus casei LC89(LC89),and Bifidobacterium longum BL21(BL21)at dose of 10~9 CFU per day for 6 weeks in male Kunming diabetic mice.Besides,the changes of gut microbiota and gene expression related to glucagon signaling pathway were detected to investigated the hypoglycemic mechanism of these three lactic acid bacteria.The results showed that compared with the mice in type 2 diabetic model group,the fasting blood glucose levels were reduced by 53.52%,57.65%and 51.64%in diabetic mice after treatment with LRa05,LC89,and BL21,respectively;the area under glucose curve and the level of fasting serum insulin were also decreased.The content of hepatic glycogen in LRa05,LC89,and BL21groups were significantly increased;LRa05,LC89 and BL21 could reduce the contents of low-density lipoprotein cholesterol(LDL-C),triglyceride(TG),and total cholesterol(TC)in the serum of diabetic mice,while LRa05,LC89 significantly increased the content of serum high-density lipoprotein cholesterol(HDL-C).The results of hematoxylin eosin staining showed that LRa05,LC89 and BL21alleviated the islet necrotic and pancreaticβ-cell damage,reduced the hepatic steatosis and vacuolization,protected crypt structure of colon.Besides,LRa05,LC89 and BL21remarkably reduced the contents of malondialdehyde(MDA),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)in the liver of diabetic mice,while significantly increased the levels of superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)in the liver of diabetic mice.The results of serum inflammatory factors showed that LRa05,LC89 and BL21 apparently reduced the serum lipopolysaccharide(LPS),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α),whereas significantly increased the level of serum interleukin-10(IL-10).The expression of ZO-1,occludin and claudin in the colon of diabetic mice were significantly increased by LRa05,LC89,and BL21,respectively.Moreover,the data also showed that these three probiotics significantly inhibited the expression of genes related to glucagon signaling pathway in the liver of diabetic mice,including glucagon(GCG),glucagon receptor(GCGR),protein kinase A(PKA),CREB-regulated transcriptional coactivator 2(CRTC2),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase).In addition,the results of gut microbiota analysis showed that LRa05,LC89 and BL21could reduce the level of Firmicutes/Bacteroidetes,Lachnospiraceae＿NK4A136＿group and Odoribacter,while raised the contents of Bacteroides in the colon of diabetic mice.In addition,both LRa05 and BL21 increased the contents of Akkermansia,and LC89 increased the contents of Alloprevotella.In conclusion,LRa05,LC89 and BL21 possess hypoglycemic activity;Notably,LC89has the best hypoglycemic effect.These probiotics could exert antidiabetic effects through regulating the gut microbiota and hepatic glucagon signaling pathway in T2DM mice. |
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