Pelargonidin-3-O-glucoside Derived from Wild Raspberry Exerts Antihyperglycemic Effect by Inducing Autophagy and Modulating Gut Microbiota

Increasing evidence indicates that anthocyanins exert beneficial effects on type 2 diabetes (T2D), but the underlying mechanism remains unclear. Herein, the hyperglycemia-lowering effect of Pg3G derived from wild raspberry was investigated on high-glucose/high-fat (HG+HF)-induced hepatocytes and db/db diabetic mice. Our results indicated that Pg3G promoted glucose uptake in HG+HF-induced hepatocytes. Moreover, Pg3G induced autophagy, whereas autophagy inhibitors blocked the hypoglycemic effect of Pg3G. Transcriptional factor EB (TFEB) was found to be linked to Pg3G-induced autophagy. In vivo study showed that Pg3G treatment contributed to the improvement of glucose tolerance, insulin sensitivity, and induction of autophagy. Furthermore, Pg3G not only modified the gut microbiota composition, as indicated by an increased abundance of Prevotella, and elevated Bacteroidetes/Firmicutes ratio, but also strengthened the intestinal barrier integrity. This study unveils a novel mechanism that Pg3G attenuates hyperglycemia through inducing autophagy and modulating gut microbiota, which implicates a potential nutritional intervention strategy for T2D.