The role of AMPK signaling pathway in the pathogenesis of type 2 diabetes mellitus with its complications and related metabolic disorders

Type 2 diabetes mellitus (T2DM) is the most common group of metabolic disorders in the world, characterized by hyperglycemia that leads to severe short-term complications such as ketoacidosis, hyperosmolar hyperglycemic coma, and long-term microvascular complications that affect the eye, kidney, and nerves. Type 2 diabetes occurs due to resistance to insulin. AMPK (adenosine monophosphate-activated protein kinase) is an energy radar that controls various metabolic and physiological processes. It is dysregulated in major chronic diseases, such as diabetes. The focus of this review is on understanding the role of AMPK in type 2 diabetes mellitus, which helps ameliorate hyperglycemia and its complications. Medications for T2DM are designed to upregulate the AMPK signaling pathway to improve its microvascular and macrovascular complications. AMPK signaling interacts with PGC-1, PI3K/Akt, NOX4, NF-κB, and other molecular pathways to produce such protective effects. Thus, AMPK is emerging as one of the most auspicious targets for both the prevention and treatment of type 2 diabetes mellitus. Hence, this review focuses on the recent evidence of the role of AMPK signaling in type 2 diabetes mellitus pathogenesis and how to circumvent its complications.