| Emerging evidence revealed that microflora may play a key role in the pathogenesis ofglycometabolic disorders. In this study, the preventive and therapic effects of Lactobacilluscasei Zhang administration on IGT rats as well as preventive effect on type2diabetes inrats were evaluated. In addition, the detailed mechanisms were explored and identified.IGT with hyperinsulinemia rats were established by feeding25%fructose solution for9-week and used for evaluating preventive and ameliorative effect of L. casei Zhang with1.0×109CFU/d intake. Rats were divided into five groups including control group(NC),preventive group (LP) and corresponding model group Ⅰ (HM)Ⅰ, therapeutic group (LT)and corresponding model group Ⅱ(HM Ⅱ). The results showed that L. casei Zhangadministration markedly exert both preventive and ameliorative effect on elevating of oralglucose tolerance AUC in IGT rats. Meanwile, intestinal numbers of Lactobacillus andBifidobacterium were significantly increased while Clostridium and liver glycogencontents were significantly decreased (p<0.05). In preventive effect, body weight, insulinand GLP-2levels were significantly lower in LP than HM ⅠIn. therapeutic effect,intestinal Bacteroides fragilis, serum osteocalcin levels and LXR-α, PPAR-γ and AdipoR2gene expression of LT were significantly higher than those in HMⅡ, while significantdecreased serum MDA levels observed in LT (p<0.05).T2DM rats induced by2-week high fat-sucrose diet with low dose of STZ injection wereused for evaluating preventive effect of L. casei Zhang with4.0×109CFU/d intake.Ratswere divided into three groups including control group(A), T2DM group (M) andpreventive group (P). The results showed that fasting and postprandial2h blood glucoselevels as well as OGTT. Meanwhile, plasma LPS levels, iNOS levels, total bile acids levelsand urea chloride ion concetration of P group were significantly lower than Mgroup(p<0.05). Pancreas injury was also alliviated in P group.SD rats induced by2-week high fat-sucrose diet for evaluating preventive effect of L.casei Zhang in the experiment2. Rats were divided into three groups including control group(CT), T2DM group (PB) and high fat-sucrose group (HF). The results showed thatindexes of PB including chloride ion concetrations (cardiac, liver, spleen and smallintestine) and chloride dependent genes mRNA and protein levels (CIC1(skeletontalmuscle), CIC2(cardiac, spleen, pancreas, renal interstitium, colon, small intestine and brainhippocampus), CIC3(liver and colon), CIC4(liver and renal interstitium), CIC5(renalinterstitium and colon), CIC7(colon), GlyRα1(liver and spleen), CYP7A1(liver and renalinterstitium), SLC26A3(renal interstitium), SLC26A6(renal interstitium), FoxA2(pancreas),GABAAα1(renal interstitium and hippocampus), BEST3(cardiac), CFTR (cardiac)) weresignificantly higher than those in HF group(p<0.05). Meanwhile, fecal primary bile acidslevels in PB were significantly lower while fecal total bile acids levels and secondarybile acids levels significantly higher than HF(p<0.05). Compared to HF group, PB ratspossess a cecum microflora characterized by low numbers of C. coccoides–E. rectalegroup, C. hylemonae-C. scindens-C. hiranonis group and C. scindens and high numbers ofLactobacillus and Bifidobacterium(p<0.05). No statistical significant differences in otherbiomarkers among these two groups.L. casei Zhang administration exert favorable preventive and therapic effects on IGT ratsas well as favorable preventive effect in the onset and development of T2DM in rats. Butthese effects may via different mechanisms. Firstly, preventive effect may be mainly due tolow absorption of fructose comply with low levels of GLP-2which was contributed tobody weight reducing and low insulin levels. Secondly, we hypothesize that increasedosteocalcin level treated with L. casei Zhang in IGT rats associated with improved glucosetolerance via one of two main vitamin K2producing strains Bacteroides fragilis. Thirdly,preventive effect of T2DM and complications by L. casei Zhang may be explained asfollows: L. casei Zhang reduce the7α-dehydroxylated activity bacteria and enhance thefecal total bile acids elimination. Thus the bile acids and chloride exchange morefrequently which induce the chloride ion infflux in organ and activiate chloride dependentproteins expression. Finally, the overall health and immunity of rats are promoted. |
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