Despite the suppressed plasma renin activity (PRA) observed in these patients, treatment with RAS inhibitors slows the progression of hypertension ( 7). In most of the cases, patients with diabetes mellitus (DM) develop hypertension, which further increases their risk of kidney disease ( 6). This system contributes to the development of hypertension by increasing intratubular angiotensin II (AngII)-dependent activation of Na + transporters and thereby stimulating tubular renal Na + reabsorption ( 4, 5). These results indicate that HG conditions promote increased levels of intratubular О±KG and OXGR1-dependent PRR upregulation, which impact AngII formation and Na + reabsorption.ДЄ hallmark of diabetic disease is the activation of the intrarenal reninвЂ“angiotensin system (RAS) ( 1вЂ“ 3). In silico analysis suggested that О±KG binds to mouse OXGR1. О±KG increases PRR expression, while treatments with ML, PKC inhibition, or intracellular Ca 2+ depletion impair this effect. Similarly, primary cultured inner medullary CD cells treated with HG showed increased PRR expression, while OXGR1 antagonist prevented this effect. Treatment with ML prevented all these effects. STZ mice had higher urinary О±KG and PRR expression along with augmented urinary AngII levels and Na + retention.

To test this hypothesis, streptozotocin (STZ)-induced diabetic mice were treated with or without montelukast (ML), an OXGR1 antagonist, for 6 days. This effect then promotes intratubular AngII formation and Na + reabsorption. We hypothesize that HG causes О±KG secretion and activation of OXGR1, which increases PRR expression in CD cells. The О±KG receptor 1 (OXGR1) is a Gq-coupled receptor expressed on the apical membrane of IC cells of the CD. However, in the CD, expression of glucose transporters is augmented, boosting the Kreb's cycle and consequently causing О±-ketoglutarate (О±KG) accumulation. In DM, the Kreb's cycle is in a state of suppression in most tissues. PRR is expressed in intercalated (IC) cells of the collecting duct (CD) and binds renin to promote angiotensin (Ang) II formation, thereby contributing to Na + reabsorption. The (pro)renin receptor (PRR) is a key regulator of renal Na + handling. 5Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United StatesДiabetes mellitus (DM) causes high glucose (HG) levels in the plasma and urine.

4Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, United States.3Laboratory of Renal Physiopathology, Institute of Biomedical Sciences, Universidad AutГіnoma de Chile, Santiago, Chile.2Department of Physiology, School of Medicine, Tulane University, New Orleans, LA, United States.1Instituto de QuГmica, Pontificia Universidad CatГіlica de ValparaГso, ValparaГso, Chile.Figueroa 3, Jorge Vivanco 1, Nicolas Salinas-Parra 1, Patricio Araos 3, Quynh My Nguyen 4, Modar Kassan 5, CristiГЎn A. AarГіn Guerrero 1 вЂ , Bruna Visniauskas 2 вЂ , Pilar CГЎrdenas 1, Stefanny M.

Ab cam duct