biostudies-literature00550Blass GU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood InstituteBLRD VANCRR NIH HHSNHLBI NIH HHSADA Foundation4296https://www.ebi.ac.uk/biostudies/studies/S-EPMC6414683biostudies-literatureUnknown9(1)Recent studies have suggested that postprandial increases in insulin directly contribute to reduced urinary sodium excretion. An abundance of research supports the ability of insulin to augment epithelial sodium channel (ENaC) transport. This study hypothesized that ENaC contributes to the increase in renal sodium reabsorption following a meal. To test this, we used fasted or 4 hour postprandial Sprague Dawley rats to analyze ENaC expression and activity. We also assessed total expression of additional sodium transporters (Na⁺-Cl^- cotransporter (NCC), Na⁺-K⁺-2Cl^- cotransporter (NKCC2), and Na⁺-K⁺-ATPase (NKA)) and circulating hormones involved in the renin-angiotensin-aldosterone system (RAAS). We found that after carbohydrate stimulus, ENaC open probability increased in split-open isolated collecting duct tubules, while ENaC protein levels remained unchanged. This was supported by a lack of change in phosphorylated Nedd4-2, an E3 ubiquitin ligase protein which regulates the number of ENaCs at the plasma membrane. Additionally, we found no differences in total expression of NCC, NKCC2, or NKA in the postprandial rats. Lastly, there were no significant changes in RAAS signaling between the stimulated and fasted rats, suggesting that acute hyperinsulinemia increases ENaC activity independent of the RAAS signaling cascade. These results demonstrate that insulin regulation of ENaC is a potential mechanism to preserve sodium and volume loss following a meal, and that this regulation is distinct from classical ENaC regulation by RAAS.Scientific reportsPostprandial Effects on ENaC-Mediated Sodium Absorption.PMC6414683HL56259R29 HL056259HL122662T32 HL134643HL116264P01 HL116264R35 HL135749HL134643R01 HL056259I01 BX0040241-15-BS-172R01 HL122662M01 RR000058HL135749Klemens CAStaruschenko APalygin OBrands MWBlass G55falsePostprandial Effects on ENaC-Mediated Sodium Absorption.Recent studies have suggested that postprandial increases in insulin directly contribute to reduced urinary sodium excretion. An abundance of research supports the ability of insulin to augment epithelial sodium channel (ENaC) transport. This study hypothesized that ENaC contributes to the increase in renal sodium reabsorption following a meal. To test this, we used fasted or 4 hour postprandial Sprague Dawley rats to analyze ENaC expression and activity. We also assessed total expression of additional sodium transporters (Na⁺-Cl^- cotransporter (NCC), Na⁺-K⁺-2Cl^- cotransporter (NKCC2), and Na⁺-K⁺-ATPase (NKA)) and circulating hormones involved in the renin-angiotensin-aldosterone system (RAAS). We found that after carbohydrate stimulus, ENaC open probability increased in split-open isolated collecting duct tubules, while ENaC protein levels remained unchanged. This was supported by a lack of change in phosphorylated Nedd4-2, an E3 ubiquitin ligase protein which regulates the number of ENaCs at the plasma membrane. Additionally, we found no differences in total expression of NCC, NKCC2, or NKA in the postprandial rats. Lastly, there were no significant changes in RAAS signaling between the stimulated and fasted rats, suggesting that acute hyperinsulinemia increases ENaC activity independent of the RAAS signaling cascade. These results demonstrate that insulin regulation of ENaC is a potential mechanism to preserve sodium and volume loss following a meal, and that this regulation is distinct from classical ENaC regulation by RAAS.2019-01-01T00:00:00Z2019 Mar2024-11-11T19:07:29.259Z2019-08-03T07:04:11ZS-EPMC64146833086290310.1038/s41598-019-40639-x