(-)-Epicatechin and the microbial 2,3-dihydroxybenzoic acid metabolite improve insulin signalling in tubular renal cells, and regulate both glucose uptake and production

Abstract

(-)-Epicatechin (EC) and main colonic phenolic acids derived from flavonoid intake, such as 2,3-dihydroxybenzoic acid (DHBA), 3,4-dihydroxyphenylacetic acid (DHPAA), 3-hydroxyphenylpropionic acid (HPPA), and vanillic acid (VA) have been suggested to exert beneficial effects in diabetes, although their mechanisms of action remain unknown. Nephropathy is a major complication of the type 2 diabetes and a leading cause of end-stage renal disease. In diabetes, renal gluconeogenesis and glucose uptake are augmented, which might be associated to increased levels of glucose transporters, and defects at the insulin signalling. Therefore, treatments aimed at improving glucose homeostasis in renal cells are considered critical against this pathology. The main goal was the evaluation of the glucose homeostasis and insulin signalling by the mentioned compounds in renal proximal tubule NRK-52E cells. EC and DHBA reduced both renal glucose uptake and production. In addition, EC and DHBA did not change the levels of SGLT-2 and GLUT-2, but regulated the expression of PEPCK via AKT, leading to a diminished glucose production. EC and DHBA also enhanced the tyrosine phosphorylation and total IR and IRS-1 levels, and activated the PI3K/AKT pathway. All these suggest that EC and DHBA modulate the renal glucose homeostasis, as regulate glucose uptake and production, and reinforce the insulin signalling through the activation of key proteins of that pathway.