Global Mapping of Flavonoids in Fruits and Vegetables: Targeting Insulin Receptors, GLP ‐ 1R , and PPARs to Mitigate Diabetes

ABSTRACT Flavonoids, bioactive compounds abundant in fruits and vegetables, have great potential as natural therapeutic agents for managing type 2 diabetes (T2D) through the modulation of key molecular targets such as insulin receptors (IRs), GLP‐1 receptors, and peroxisome proliferator‐activated receptors. This paper aims to provide an in‐depth review of the flavonoids found in various fruits and vegetables and the musculoskeletal mechanisms underlying their therapeutic potential in addressing diabetes through interactions with IRs, GLP‐1/R, and PPARs. A systematic search was conducted across major databases, including PubMed, Scopus, Web of Science, Cochrane Library, and Embase. A combination of a comprehensive literature review approach and in silico analysis revealed that the compounds such as hesperidin, quercetin, luteolin and genistein showed significant affinity for these targets, even exceeding those of some conventional drugs such as metformin. These findings not only reinforce the scientific evidence on the benefits of flavonoid compounds in improving insulin sensitivity and regulating glucose and lipid metabolism, but also open up opportunities for the development of more sustainable and affordable nutrition‐based therapies. It is important to acknowledge, however, that while promising, further high‐quality studies, including large‐scale clinical trials, are needed to firmly establish the clinical efficacy and optimal application of these flavonoid‐based interventions in human populations. In addition, the study will also highlight the importance of an interdisciplinary approach between pharmacology, nutrition, and computational technology in facing evolving public health challenges.