The Galectin-3 Paradox: A Review Stating Perspectives from the Standpoint of Inflammatory Processes in Insulin Resistance

Insulin resistance (IR) forms the core of a wide spectrum of metabolic disorders, including Type 2 Diabetes Mellitus (T2DM), Non Alcoholic Fatty Liver Disease (NAFLD; presently known as Metabolic Dysfunction-Associated Steatotic Liver Disease or MASLD), and cardiovascular complications. Despite the inroads made in comprehending IR, the underlying role of chronic lowgrade inflammation in the pathogenesis remains to be unequivocally established. Galectin-3 (Gal-3), is a β-galactoside-binding lectin with documented roles in fibrosis and immune regulation. Gal-3 has recently been figuring in worldwide studies as a key inflammatory mediator associated with IR. Paradoxically, while elevated Galectin-3 levels associate with IR and metabolic dysfunction, experimental evidence suggests a protective role depending on the tissue context and the phase or degree of disease progression. The present review succinctly examines the paradoxical behaviour of Galectin-3 in IR and is based on the documented literature available in established databases, including PubMed, Scopus and Web of Science. The review endeavours earnestly to evaluate the impact of Gal-3 on organ dysfunction and hepatic insulin signalling disruption. Its influence on adipose tissue remodelling, skeletal and cardiac muscle resistance, retinal complications, and peripheral neuropathy was also explored. The article further highlights current challenges in IR diagnosis and strives to discuss the role of emerging biochemical markers. Understanding the dualistic role of Galectin-3 could herald the arrival of novel therapeutic strategies targeting inflammation-driven IR.