The influence of insulin and incretin-based therapies on renal tubular transport

Abstract The tubular function of the kidney is very complex and is finely regulated by many factors. These include a variety of hormonal signaling pathways which are involved in the expression, activation and regulation of renal transporters responsible for the handling of electrolytes. Glucose-lowering drugs such as insulin and incretin-based therapies, exert a well-known renal protective role in diabetic kidney disease, mainly acting at the glomerular level. In the literature, several studies have described the effect of insulin and the incretin hormones on tubular transport. Most of these studies focused on the variations in excretion and clearance of sodium but did not extensively and systematically investigate the possible variations that these hormones may induce in the tubular regulation of all the other electrolytes, urea metabolism, acid–base balance and urinary pH. While insulin action on the kidney is very well-described, the renal tubular impact of incretin-based therapies is less consistent and the results available are scarce. To our knowledge, this is the first review summarizing the effects induced on renal tubules by insulin, glucagon-like peptide-1 (GLP-1) receptor agonists and serine protease dipeptidyl peptidase-4 (DPP4) inhibitors in both healthy and diabetic human subjects. This is significant because it highlights the existence of a renal-gut and pancreas axis which also has a direct tubular effect and enables a deeper understanding of renal physiology. Graphical abstract