Hypoglycemic and Gut Microbiota-Modulating Effects of Pectin from <i>Citrus aurantium</i> “Changshanhuyou” Residue in Type 2 Diabetes Mellitus Mice

To fully utilize the <i>Citrus aurantium</i> "Changshanhuyou" resource, the hypoglycemic effect and mechanisms of action of pectin from Changshanhuyou residue (HYP) were studied. HYP considerably inhibited α-glucosidase, suggesting its potent in vitro hypoglycemic activity. In streptozotocin-induced type 2 diabetes mellitus (T2DM) mice, HYP significantly increased the body weight, survival rate, hexokinase activity, and glycogen content and decreased fasting blood glucose, oral glucose tolerance, liver weight, and glycated serum protein levels. Furthermore, HYP remarkably improved glycolipid metabolism-related indices in both serum and liver, IL-6 and TNF-α levels in serum, and antioxidant enzyme activities in liver. HYP also modulated mRNA expression of the key factors (e.g., Akt, PI3K, IRS2, InsR, GLUT4, G6 Pase, PEPCK, AMPK, GS, and GSK-3β) and increased short chain fatty acid production and abundance of beneficial bacteria. Thus, the underlying hypoglycemic mechanism of HYP may involve the activation of PI3K/Akt, AMPK, and GS/GSK-3β signaling pathways and modulation of gut microbiota composition.