This study conducted in vivo and in situ experiments with rats to investigate the glucagon-like peptide-1 (GLP-1) secretion in response to oral or ileal administration of α-glucosyl-isoquercitrin (20-40 mmol in 2 mL; Q3G), fructooligosaccharides (200 mmol in 2 mL; FOS) and Q3G + FOS. Direct effects on GLP-1-producing l-cells were also examined by an in vitro study using a murine enteroendocrine cell line, GLUTag. To evaluate the plasma GLP-1 level, blood samples from jugular cannula for in vivo and portal cannula for in situ experiments were obtained before and after administration of Q3G, FOS, or Q3G + FOS. We found tendencies for increases but transient stimulation of GLP-1 secretion by Q3G in in vivo and in situ experiments. Although FOS alone did not have any effects, Q3G + FOS enhanced and prolonged high plasma GLP-1 level in both experiments. In addition, application of Q3G on GLUTag cells stimulated GLP-1 secretion while FOS enhanced the effect of Q3G. Our results suggest that Q3G + FOS possess the potential for the management or prevention of Type 2 diabetes mellitus (T2DM) by enhancing and prolonging the GLP-1 secretion via direct stimulation of GLP-1 producing l-cell.
Q3G + FOS diet improved glucose tolerance, insulin sensitivity, and total cholesterol level with increasing GLP-1 secretion and a higher level of blood quercetin. Q3G + FOS may reduce the risk of T2DM.
Glucagon‐like peptide‐1 (GLP‐1), which is released from the enteroendocrine cells in the presence of glucose, has shown to improve glucose tolerance. Fructooligosaccharides (FOS) and α‐ glucosyl‐isoquercitrin (Q3GM) also improve glucose metabolism but its effect on the role of GLP‐1 is unclear and warrants further investigation. We used two groups of rats (i.e., conscious and anesthetized) to conduct in vivo and in situ experiments, respectively, to investigate the secretion of GLP‐1 post administering Q3GM with‐ and without FOS. Baseline blood samples were obtained via jugular vein for in vivo but portal vein for in situ rat group with subsequent samples obtained at 15, 30, 60, 90 and 120 minutes to evaluate plasma GLP‐1 levels by using ELISA. We examined the differences among groups with 2‐way ANOVA with post‐hoc Tukey‐Kramer's test for GLP‐1 level among the group and Dunnett's for the differences from the basal blood sample. We found that for both in vivo and in situ experiments, Q3GM without FOS stimulated the secretion of GLP‐ 1, transiently. On the contrary, Q3GM with FOS significantly enhanced and prolonged plasma GLP‐1 concentrations increased by Q3GM in both in vivo and in situ experiments. Our results suggest that Q3GM with FOS has the potential for prevention or treatment of type 2 diabetes by enhancement of GLP‐1 secretion and prolongation the high plasma concentration of the antidiabetic hormone.Grant Funding Source: Hokkaido University
An enhancement FOS on improvement of glucose tolerance and insulin sensitivity by a flavonoid glycoside, Q3G, and their mechanisms were studied. Rats were fed a sucrose‐based diet with or without 0.3% Q3G, 5% FOS, or 0.3% Q3G+5% FOS, while dextrin‐based diet was used for a normal reference group. OGTTs were conducted on day 14, 28, 45. Flavonoid levels in the aortic blood were measured by LC/MS. Body weight gain was lowered in Q3G+FOS group without changes in food intake. Abdominal fat weights and cecal pH were reduced in both the FOS‐fed groups without any effects of Q3G. Combination of Q3G and FOS only reduced blood glucose levels at 60 min in all OGTTs. HOMA‐IR showed an improvement in the Q3G+FOS group on day 14 and 28. On day 45, the value was improved in the individual FOS or Q3G group, and was further improved in the FOS+Q3G group. A much higher blood level of quercetin was observed in the FOS+Q3G group compared with the Q3G group, which may contribute the combination effects of Q3G and FOS. Secretion of GLP‐1 observed in the small intestinal loops of anesthetized rats and in vivo experiment were increased by addition of quercetin to luminal fluid containing FOS. This may involve in the improvement of glucose tolerance. In conclusion, FOS increases bioavailability of Q3G, and enhanced beneficial effects of Q3G on glucose tolerance and insulin sensitivity, which have a potential for prevention of type 2 diabetes.Grant Funding Source : Graduate School of Agriculture, Hokkaido University
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