Effects of Berberine on Insulin-Sensitive Tissues: Nutrient-Derived Modulator of Metabolic Disease

Insulin-sensitive tissues, including skeletal muscle, adipose tissue, and liver, are central regulators of systemic glucose and lipid homeostasis. Insulin signaling disruption in these tissues is a key pathological feature underlying insulin resistance and contributes to the development of metabolic disorders such as type 2 diabetes mellitus (T2DM), obesity, and liver disease. Increasing evidence suggests that berberine (BBR), a naturally occurring isoquinoline alkaloid derived from Berberis species, attenuates insulin resistance and exhibits antidiabetic, lipid-lowering, and anti-inflammatory properties across multiple metabolic tissues. This review analyzes current in vitro, in vivo, and clinical data examining the effects of BBR in insulin-sensitive tissues. In skeletal muscle, BBR promotes glucose consumption while in adipose tissue, it attenuates adipogenesis, lipid accumulation and inflammation. In hepatic tissue, BBR suppresses gluconeogenesis, improves lipid metabolism and reduces hepatic steatosis. Clinical trials report reductions in fasting glucose, serum lipids, visceral adiposity, and hepatic fat content. Collectively, current evidence indicates that BBR exerts multi-tissue insulin-sensitizing effects with therapeutic potential for metabolic disease. However, mechanistic human data directly linking tissue-specific actions remain limited. Future clinical studies incorporating tissue-specific metabolic assessments, dose–response analyses, metabolomic profiling, and consideration of sex- and age-related variability are warranted to fully elucidate its clinical efficacy.