Effect of Renal Tubule-Specific Knockdown of the Na+/H+ Exchanger NHE3 in Akita Diabetic Mice.

Effect of Renal Tubule-Specific Knockdown of the Na+/H+ Exchanger NHE3 in Akita Diabetic Mice. Am J Physiol Renal Physiol. 2019 Jun 05;: Authors: Onishi A, Fu Y, Darshi M, Crespo-Masip M, Huang W, Song P, Patel R, Kim YC, Nespoux J, Freeman B, Soleimani M, Thomson SC, Sharma K, Vallon V Abstract NHE3 contributes to Na+/bicarbonate reabsorption and ammonium secretion in early proximal tubules. To determine its role in the diabetic kidney, type 1 diabetic Akita mice with tubular NHE3 knock-down (Pax8-Cre; NHE3-KO) were generated. NHE3-KO had higher urine pH, more bicarbonaturia, and compensating increases in renal mRNA expression for genes associated with generation of ammonium, bicarbonate and glucose (phosphoenolpyruvate carboxykinase-PEPCK) in proximal tubules and proton and ammonia secretion and glycolysis in distal tubules. This left blood pH and bicarbonate unaffected in non-diabetic and diabetic NHE3-KO versus wild-type mice, but was associated with renal upregulation of pro-inflammatory markers. Higher renal PEPCK expression in NHE3-KO was associated with lower SGLT2 and higher SGLT1 expression, indicating a downward tubular shift in sodium and glucose reabsorption. NHE3-KO was associated with lesser kidney weight (KW) and GFR independent of diabetes and prevented diabetes-associated albuminuria. NHE3-KO, however, did not attenuate hyperglycemia or prevent diabetes from increasing KW and GFR. Higher renal gluconeogenesis may ex...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research