Abstract
Diabetes mellitus is a complex metabolic disorder and is considered a fast-growing global health problem. Type 2 diabetes (T2D) represents the majority of total diabetes prevalence and β-cell dysfunction has been described as a crucial point for this disease development and progression. To date, all of the common anti-hyperglycaemic drugs used for diabetes management cause undesirable side effects or problems with long-term efficacy or safety and the development of alternative approaches for the prevention as well as for the treatment of T2D might be a valuable solution to meet this rising demand. In this regards, numerous epidemiological studies indicate that exposure to certain polyphenol compounds is associated with the prevention of chronic diseases, including diabetes. Here, we review growing evidence suggesting that polyphenols can modulate the activity of various molecular targets, which are known to control β-cell function, involved in the development and the progression of this diabetes. The protective effects of polyphenols on β-cell function is reported with a particular focus on the mechanism of action behind polyphenol putative bioactivity. Animal and in vitro studies selected in this review, reporting about both flavonoid and non-flavonoid compounds, highlight the direct action of polyphenols on pancreatic β-cells, stimulating insulin secretion through the activation of specific cellular targets and protecting these cells from damages mediated by oxidative stress and inflammation, both typically elevated in diabetes. Some of the reviewed studies describe polyphenol effects comparable to those exerted by many drugs commonly used in diabetes treatment, and, in some occasions, synergistic polyphenol-drug interactions. Finally, future studies need to be addressed to the effects of specific polyphenol human and microbial metabolites, which are still poorly studied, in order to better define the preventive and therapeutic approach to contrast β-cell failure and diabetes progression.