AMP-activated protein kinase regulation of kidney tubular transport

The coupling of epithelial transport to underlying metabolic status is critical because solute transport processes normally consume a large proportion of total cellular energy. Recently, AMP-activated protein kinase (AMPK) has emerged as a critical transport regulator in tissues throughout the body. This review summarizes the role of AMPK in the regulation of renal epithelial transport, updates the growing list of AMPK transport protein targets and regulatory mechanisms, and discusses the potential clinical significance of this regulation in normal and disease states.

Recent work has identified several new ion channels, transporters, and pumps that are regulated by AMPK in the kidney, and a better understanding of the mechanisms for the AMPK-dependent regulation of membrane transport proteins is emerging. Treatment with AMPK activators may be beneficial in preventing deleterious effects in the kidney in the setting of various diseases, including acute ischemia, diabetes mellitus and polycystic kidney disease, via mechanisms that depend at least partly on the regulatory effects of AMPK on solute transport.

The energy-sensing kinase AMPK has a growing list of pleiotropic effects on cells and tissues, including its key role in the coupling of membrane transport to metabolic status in epithelial tissues like the kidney. AMPK is also involved in the coordination of hormonal, inflammatory, and other cellular stress pathway signals to produce an integrated effect on tubular transport. Identifying and characterizing new transport protein targets of AMPK should yield valuable new insights into various physiological and pathological processes in the kidney.