Objective To investigate the effect of Dendrobium officinale polysaccharide (DOP) on prediabetes (PDM) and explore its mechanism in improving PDMs through the gut short-chain fatty acids (SCFAs)-G protein-coupled receptor 43 (GPR43)-glucagon-like peptide 1 (GLP1) pathway. Methods SD Rats were randomly divided into control group, model group and DOP low-, high-dose (0.1, 0.2 g/kg) groups, with 10 rats in each group. Except for the control group, the remaining rats were fed a high-sugar and high-fat diet for six weeks to establish a PDM model. During the modeling period, the corresponding drugs were administered intravenously, and the control group and model group were given distilled water of equal volume. Changes in general physiological indicators, glucose/lipid levels, glucose regulation function, intestinal/pancreatic histopathology, fecal SCFAs contents, expressions of GPR43 and GLP1 and its receptor in intestinal/pancreatic were analyzed. Results Compared with model group, DOP significantly increased tail microcirculatory blood flow in PDM rats (P < 0.01) and decreased anal temperature (P < 0.01), significantly reduced levels of total cholesterol and low-density lipoprotein cholesterol in serum (P < 0.05, 0.01), significantly decreased the oral glucose tolerance test results, fasting blood glucose, 2 h postprandial glucose, homeostasis model assessment-insulin resistance index, and C-peptide levels in PDM rats (P < 0.05, 0.01), increased the insulin sensitivity index (P < 0.05), and alleviated the pathological damage of pancreas, ileum and colon. Gas chromatography results showed that DOP administration could significantly increase the levels of acetic acid, butyric acid, isovaleric acid and SCFAs in feces (P < 0.05, 0.01). ELISA, Western blotting and qRT-PCR results showed that DOP administration could significantly increase the plasma GLP1 level, as well as the mRNA and protein expressions of GPR43 and GLP1 receptor in ileum and pancreas (P < 0.05, 0.01). Conclusion DOP could improve PDM, and its effect may be related to enhancing gut-derived SCFA production, up-regulating GPR43 expressions in intestine and pancreas, subsequent promoting GLP1 secretion, restoring β-cell function and improving glucose regulation.

Dendrobium officinale polysaccharide  /  prediabetes  /  short-chain fatty acids  /  G protein-coupled receptors 43  /  glucagon-like peptide 1