Pumpkin Soluble Dietary Fiber instead of Insoluble One Ameliorates Hyperglycemia via the Gut Microbiota–Gut–Liver Axis in db/db Mice

Pumpkin extract has been shown to alleviate hyperglycemic symptoms by improving glucose metabolism disorders. However, the specific active components responsible for its hypoglycemic effects and the underlying molecular mechanisms remain unclear. In this study, db/db mice underwent a 4-week dietary intervention with two pumpkin flours (PF1 and PF2), total dietary fiber (TDF), soluble dietary fiber (SDF), and insoluble dietary fiber (IDF), with acarbose serving as a positive control. Our results revealed that pumpkin components significantly altered the gut microbiota, characterized by a reduction in diabetes-related bacteria and an increase in short-chain fatty acid (SCFA)-producing bacteria, including <i>Bacteroides</i>, <i>Akkermansia</i>, and <i>Lachnospiraceae_NK4A136</i> group. Additionally, pumpkin components significantly increased fecal SCFA levels and upregulated the expression of SCFA receptor GPR43, potentially promoting GLP-1 secretion. Notably, pumpkin components significantly reduced fasting blood glucose and serum insulin levels and inhibited gluconeogenesis. This effect may be ascribed to the inhibition of the cAMP/PKA/CREB signaling pathway coupled with the activation of the PI3K/AKT signaling pathway. Our research indicated that pumpkin flour and dietary fiber alleviated hyperglycemia through the gut-liver axis, with SDF contributing the most to the hypoglycemic effect. These findings suggest that pumpkin components may serve as an adjunct nutritional intervention to ameliorate hyperglycemia.