Thiazolidinediones (TZDs) are widely used to treat type-2 diabetes, but their use is complicated by systemic fluid retention. A paper in the August 2005 issue of Nature Medicine discloses the mechanism underlying this side effect.
In the kidney, the pharmacological target of TZDs, peroxisome proliferator-activated receptor-gamma (PPARg), is most abundant in the collecting duct of the nephron --the filtering unit of the kidney. Matthew Breyer and colleagues show that mice treated with TZDs retain water, an effect that was blocked by selective deletion of PPARg from the collecting duct. Deletion of PPARg decreased the transport of sodium through the sodium-selective channel Enac-g.
This study identifies Enac-g as a PPARg target in the collecting duct, suggesting that selective blockers of this channel might provide a specific therapy against fluid retention, an undesirable side effect of TZDs.
Matthew Breyer (Vanderbilt University, Nashville, TN, USA)
Also published online.
(C) Nature Medicine press release.
Message posted by: Trevor M. D'Souza