Insights into the regulation of podocyte and glomerular function by lactate and its metabolic sensor G-protein-coupled receptor 81.

Abstract

Podocytes and their foot processes are an important cellular layer of the renal filtration barrier that is involved in regulating glomerular permeability. Disturbances of podocyte function play a central role in the development of proteinuria in diabetic nephropathy. The retraction and effacement of podocyte foot processes that form slit diaphragms are a common feature of proteinuria. Correlations between the retraction of foot processes and the development of proteinuria are not well understood. Unraveling peculiarities of podocyte energy metabolism notably under diabetic conditions will provide insights into the pathogenesis of diabetic nephropathy. Intracellular metabolism in the cortical area of podocytes is regulated by glycolysis, whereas energy balance in the central area is controlled by oxidative phosphorylation and glycolysis. High glucose concentrations were recently reported to force podocytes to switch from mitochondrial oxidative phosphorylation to glycolysis, resulting in lactic acidosis. In this review, we hypothesize that the lactate receptor G-protein-coupled receptor 81 (also known as hydroxycarboxylic acid receptor 81) may contribute to the control of podocyte function in both health and disease.