The role of AMP-activated protein kinase activators on energy balance and cellular metabolism in type 2 diabetes mellitus

Abstract

Type 2 Diabetes Mellitus (T2DM) is a growing health concern that leads to increased morbidity and mortality rates worldwide. A protein complex called AMP-activated protein kinase (AMPK) regulates energy balance within cells and controls cellular metabolism. Over the past decade, numerous studies have highlighted the remarkable potential of AMPK and its activators in treating T2DM. Key compounds, including biguanides (e.g., metformin), thiazolidinediones, phenolic compounds (e.g., resveratrol), and AICAR, have demonstrated the ability to improve insulin sensitivity, enhance glucose uptake in skeletal muscle, reduce hepatic glucose production, and improve glycemic control. Additionally, AMPK activators have shown promising effects on lipid metabolism, inflammation, and oxidative stress, which are critical factors in the pathogenesis of T2DM. The activation of AMPK by natural products and synthetic drug candidates represents a promising avenue for developing novel treatments targeting T2DM and its complications. This review aims to provide an overview of direct and indirect AMPK activation and its relevance in organs implicated in the development of T2DM.