Polyphenols and Insulin Sensitivity: A Pathophysiological Perspective

Polyphenols, a diverse group of naturally occurring compounds found in plants, have garnered attention for their potential role in modulating insulin sensitivity. With the increasing prevalence of insulin resistance and type 2 diabetes mellitus (T2DM), understanding the mechanisms by which polyphenols influence glucose metabolism is essential. These bioactive compounds exert their effects through multiple pathways, including reduction of oxidative stress, suppression of pro-inflammatory cytokines, and modulation of key metabolic regulators such as AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptors (PPARs). Additionally, polyphenols influence gut microbiota composition, promoting beneficial microbial populations that enhance insulin signaling. Their antioxidant and anti-inflammatory properties help restore insulin sensitivity by mitigating reactive oxygen species (ROS) and chronic low-grade inflammation. Furthermore, polyphenols regulate lipid metabolism, reducing free fatty acid accumulation, which is a significant contributor to insulin resistance. Despite promising preclinical evidence, clinical trials yield mixed results, largely due to differences in bioavailability and individual metabolic responses. Future research should focus on optimizing polyphenol formulations and understanding interindividual variability to harness their full therapeutic potential. Keywords: Polyphenols, insulin resistance, oxidative stress, AMPK, gut microbiota