We also found that 3DG-treated rats displayed obviously pancreatic islet cell dysfunction that is one of the typical characteristic of T2DM. exposured to 3DG. Results 3DG treatment for 2?weeks increased 3DG content of intestinal tissues, fasting blood glucose concentration, and reduced plasma concentrations of GLP-1 and insulin at fasting and 15 and 180?min Isosorbide Mononitrate after Isosorbide Mononitrate the glucose load and oral glucose tolerance in conjunction with increased plasma glucagon concentrations. The expressions of TAS1R2, TAS1R3 and TRPM5 were shown to be reduced whereas 3DG treatment did not affect plasma dipeptidyl peptidase-4 activity, indicating an impaired GLP-1 secretion in 3DG-treated rats. This idea was further supported by the fact that exposure to 3DG directly decrease GLP-1 secretion in STC-1. Conclusion It is the first demonstration that 3DG was capable of accumulating in intestinal tissue and thereby decreased secretion of GLP-1 and insulin in a similar manner. 3DG-treated rats developed impaired glucose regulation (IGR) with obviously pancreatic islet cell dysfunction. It is further concluded that a decrease in the biological function of GLP-1 resulting from the decreased GLP-1 secretion is the most likely mechanism for the impaired insulin secretion, which?ultimately Isosorbide Mononitrate promoted the development of IGR. These results will also contribute to a better understanding of the significance for restoring physiological GLP-1 secretion. Electronic supplementary material The online version of this article (doi:10.1186/s13098-016-0194-9) contains Isosorbide Mononitrate supplementary material, which is available to authorized users. for 5?min at 4?C to remove any floating cells. GLP-1 concentration in the supernatant was measured by ELISA (Millipore, MA, USA). Statistical analysis Results of the experimental studies are expressed as mean??SD. Statistical significance of differences was analyzed by the Students t test or One-way analysis of variance. All p values 0.05 were considered statistically significant. Results Increased 3DG contents in intestinal tissues of rats 2?weeks after intragastric administration of 3DG Since lower absorption rate of 3DG has been indicated in in a single administration study , we further assess whether 3DG is capable of accumulating in intestinal tissue after continuous oral administration of 3DG. After intragastric administration of 50?mg/kg 3DG for 2?weeks, 3DG levels were increased significantly in the upper small intestine (1.4-fold), lower small intestine (1.4-fold), ileum (1.4-fold) and colon (twofold) compared with the basal levels in the corresponding control group. The colon had the greatest increase in the level of 3DG compared with control and had the highest levels among the tissue tested (Fig.?1a). Colon 3DG level was increased dependent on the concentration of 3DG administrated (Fig.?1b). A certain amount of 3DG in intestinal tissue of control rats may originate from intake of exogenous 3DG and production of 3DG in gut, which should be examined in a following study. These observations suggest that 3DG is usually capable of accumulating in intestinal tissue after long-term regularly intake of dietary 3DG. Open in a separate windows Fig.?1 Increased 3DG contents in intestinal tissues of rats 2?weeks after intragastric administration of 3DG, em n /em ?=?6 for each group. The upper small intestine, lower small intestine, ileum (a) and colon (b) 3DG levels were measured by HPLC after 2-week administration of 3DG or vehicle. Values are mean??SD. * em p /em ? ?0.05, ** em p /em ? ?0.01 compared with control group Intragastric administration of 3DG for 2?weeks led to a decrease in GLP-1 secretion in rats In concern of the well-known relationship between increasing endogenous GLP-1 secretion and improved glucose tolerance, secretion of the gut hormone GLP-1 has been Isosorbide Mononitrate suggested to be impaired in T2DM and in conditions associated with hyperglycemia. We next decided whether 2-week intragastric administration of Rabbit Polyclonal to OR10A7 3DG as an independent factor for the.