Type 2 diabetes (T2D) is a fast-increasing health problem globally, and it results from insulin resistance and pancreatic β-cell dysfunction. The gastrointestinal (GI) tract is recognized as one of the major regulatory organs of glucose homeostasis that involves multiple gut hormones and microbiota. Notably, the incretin hormone glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L-cells plays a pivotal role in maintaining glucose homeostasis via eliciting pleiotropic effects, which are largely mediated via its receptor. Thus, targeting the GLP-1 signaling system is a highly attractive therapeutic strategy to treatment T2D. Polyphenols, the secondary metabolites from plants, have drawn considerable attention because of their numerous health benefits, including potential anti-diabetic effects. Although the major targets and locations for the polyphenolic compounds to exert the anti-diabetic action are still unclear, the first organ that is exposed to these compounds is the GI tract in which polyphenols could modulate enzymes and hormones. Indeed, emerging evidence has shown that polyphenols can stimulate GLP-1 secretion, indicating that these natural compounds might exert metabolic action at least partially mediated by GLP-1. This review provides an overview of nutritional regulation of GLP-1 secretion and summarizes recent studies on the roles of polyphenols in GLP-1 secretion and degradation as it relates to metabolic homeostasis. In addition, the effects of polyphenols on microbiota and microbial metabolites that could indirectly modulate GLP-1 secretion are also discussed.
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