| Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat. | |
| | |
MedLine Citation:
|
PMID: 21940401 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Tubuloglomerular feedback (TGF) stabilizes nephron function from minute to minute and adapts to different steady-state inputs to maintain this capability. Such adaptation inherently renders TGF less efficient at buffering long-term disturbances, but the magnitude of loss is unknown. We undertook the present study to measure the compromise between TGF and TGF adaptation in transition from acute to chronic decline in proximal reabsorption (Jprox). As a tool, we blocked proximal tubule sodium-glucose cotransport with the SGLT2 blocker dapagliflozin in hyperglycemic rats with early streptozotocin diabetes, a condition in which a large fraction of proximal fluid reabsorption owes to SGLT2. Dapagliflozin acutely reduced proximal reabsorption leading to a 70% increase in early distal chloride, a saturated TGF response, and a major reduction in single nephron glomerular filtration rate (SNGFR). Acute and chronic effects on Jprox were indistinguishable. Adaptations to 10-12 days of dapagiflozin included increased reabsorption by Henle's loop, which caused a partial relaxation in the increased tone exerted by TGF that could be explained without desensitization of TGF. In summary, TGF contributes to long-term fluid and salt balance by mediating a persistent decline in SNGFR as the kidney adapts to a sustained decrease in Jprox. |
| | |
Authors:
|
Scott C Thomson; Timo Rieg; Cynthia Miracle; Hadi Mansoury; Jean Whaley; Volker Vallon; Prabhleen Singh |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-09-21 |
Journal Detail:
|
Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 302 ISSN: 1522-1490 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2011-12-26 Completed Date: 2012-03-26 Revised Date: 2012-05-23 |
Medline Journal Info:
|
Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: R75-83 Citation Subset: IM |
Affiliation:
|
Department of Medicine, University of California and Veterans Affairs San Diego Healthcare System, 92161, USA. sthomson@ucsd.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Diabetes Mellitus, Experimental / chemically induced, physiopathology* Disease Models, Animal Feedback, Physiological / drug effects, physiology Glomerular Filtration Rate / drug effects, physiology Glucosides / pharmacology Homeostasis / drug effects, physiology Kidney Glomerulus / drug effects, physiology* Kidney Tubules / drug effects, physiology* Male Rats Rats, Wistar Sodium-Glucose Transporter 2 / antagonists & inhibitors*, physiology Streptozocin / adverse effects |
| Grant Support | |
ID/Acronym/Agency:
|
K08 DK084305/DK/NIDDK NIH HHS; R01 DK056248/DK/NIDDK NIH HHS; R01-DK-56248/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; 0/Glucosides; 0/Sglt2 protein, rat; 0/Sodium-Glucose Transporter 2; 18883-66-4/Streptozocin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A novel vascular EET synthase: role of CYP2C7.
Next Document: Cannabinoid and GABA modulation of sympathetic nerve activity and blood pressure in the dorsal peria...