Hypoglycemic effects and associated mechanisms of resveratrol and related stilbenes in diet

Hyperglycemia has become a global health problem due to changes in diet and lifestyle. Most importantly, persistent hyperglycemia can eventually develop into type II diabetes. While the usage of current drugs is limited by their side effects, stilbenes derived from fruits and herbal/dietary plants are considered as important phytochemicals with potential hypoglycemic properties. Herein, the most common stilbenoids in consumed foods, i.e. resveratrol, pterostilbene, piceatannol, oxyresveratrol, and 2,3,5,4′-tetrahydroxystilbene-2-O-β-glucopyranoside (THSG), are reviewed in this paper. These stilbenes are found to regulate glucose homeostasis via (a) modulation of feeding behaviour and nutrition absorption; (b) restoration of insulin signalling by enhancing insulin production/insulin sensitivity; (c) improvement of gut permeability, gut microbial profile and resulting metabolomes; and (d) amelioration of circadian rhythm disruption. In this review, we have summarized the underlying mechanisms for the hypoglycemic effects of the five most common dietary stilbenoids listed above, providing a comprehensive framework for future study and applications.