Thiazolidinediones or TZD drugs which are widely used in diabetes treatment have shown serious effects on the kidneys that lead to fluid retention as the volume of plasma in the bloodstream expands.
The drugs have effects on the kidneys that lead to fluid retention as the volume of plasma in the bloodstream expands.
"TZDs usually increase body weight by several kilograms," said George Seki of the University of Tokyo.
"However, TZDs sometimes cause massive volume expansion, resulting in heart failure," he added.
Now his team reports that those negative consequences arise in more than one way.
TZDs act on a hormone receptor known as peroxisome proliferator-activated receptor ? (PPAR?). PPAR? is a master gene of fat cell biology and differentiation, Seki explained, making it an ideal target for diabetes treatment.
Seki's team has found that TZDs also have direct effects on channels in the kidney known as the proximal tubules.
TZDs rapidly stimulate sodium-coupled bicarbonate absorption from renal proximal tubules. Inhibitors of PPAR? or other players in the pathway suppress that stimulation, they report.
The researchers confirm that those effects occur regardless of whether PPAR? can bind DNA to influence the activity of other genes.
The study has been published in the issue of Cell Metabolism, a Cell Press publication.