Berberine and type 2 diabetes mellitus: a natural alkaloid with therapeutic benefits?

Abstract

Type 2 diabetes mellitus (T2DM) represents a major and widespread metabolic disorder affecting millions of people worldwide. A key mechanism underlying the onset and progression of T2DM is insulin resistance.The main causes of insulin resistance are a sedentary lifestyle and obesity. Obesity promotes adipose tissue inflammation by increasing immune cell infiltration and inflammatory mediator production, alters gut microbiota toward a pro-inflammatory profile, and induces metabolic endotoxemia, resulting in low-grade systemic inflammation. Together with oxidative stress and elevated free fatty acids, these processes promote insulin resistance, hepatic gluconeogenesis, and pancreatic β-cell dysfunction, thereby exacerbating T2DM. Interestingly, berberine, which is a natural alkaloid with antioxidant and anti-inflammatory properties, affects all of the aforementioned events, thereby potentially contributing to the alleviation of insulin resistance and improvement of T2DM. This article provides a thorough narrative review of the available mechanistic and clinical evidence regarding the potential effects of berberine on T2DM by integrating findings from in vitro, animal, and clinical studies. In addition, this review critically examines the limitations, and translational relevance of the existing evidence. It also discusses the current status of berberine-containing pharmaceutical and nutraceutical formulations and highlights key pharmaceutical and translational challenges. The available evidence indicates that berberine has the potential to influence multiple pathogenic pathways implicated in T2DM and may thereby improve insulin sensitivity. Nevertheless, most mechanistic evidence remains preclinical, and further formulation standardization together with well-designed clinical trials are required to define its efficacy, safety, and optimal dosing before routine clinical use.