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Increased susceptibility of db/db mice to rosiglitazone-induced plasma volume expansion: role of dysregulation of renal water transporters
- Source :
- American Journal of Physiology-Renal Physiology. 305:F1491-F1497
- Publication Year :
- 2013
- Publisher :
- American Physiological Society, 2013.
-
Abstract
- Thiazolidinediones (TZDs), which are synthetic peroxisome proliferator-activated receptor subtype-γ (PPARγ), agonists are highly effective for treatment of type 2 diabetes. However, the side effect of fluid retention has significantly limited their application. Most of the previous studies addressing TZD-induced fluid retention employed healthy animals. The underlying mechanism of this phenomenon is still incompletely understood, particularly in the setting of disease state. The present study was undertaken to examine rosiglitazone (RGZ)-induced fluid retention in db/db mice and to further investigate the underlying mechanism. In response to RGZ treatment, db/db mice exhibited an accelerated plasma volume expansion as assessed by hematocrit (Hct) and fluorescent nanoparticles, in parallel with a greater increase in body weight, compared with lean controls. In response to RGZ-induced fluid retention, urinary Na+ excretion and urine volume were significantly increased in lean mice. In contrast, the natriuretic and diuretic responses were significantly blunted in db/db mice. RGZ db/db mice exhibited a parallel decrease in plasma Na+ concentration and plasma osmolality, contrasting to unchanged levels in lean controls. Imunoblotting analysis showed downregulation of renal aquaporin (AQP) 2 expression in response to RGZ treatment in lean mice but not in db/db mice. Renal AQP3 protein expression was unaffected by RGZ treatment in lean mice but was elevated in db/db mice. In contrast, the expression of Na+/H+ exchanger-3 (NHE3) and NKCC2 was unchanged in either mouse strain. Together these results suggest that compared with the lean controls, db/db mice exhibited accelerated plasma volume expansion that was in part due to the inappropriate response of renal water transporters.
- Subjects :
- Blood Glucose
Male
medicine.medical_specialty
Sodium-Hydrogen Exchangers
Physiology
Body water
Water-Electrolyte Imbalance
Natriuresis
Diuresis
Hematocrit
Kidney
Weight Gain
Rosiglitazone
Excretion
Mice
Body Water
Internal medicine
Diabetes Mellitus
medicine
Animals
Humans
Hypoglycemic Agents
Plasma Volume
Triglycerides
Solute Carrier Family 12, Member 1
Aquaporin 3
Aquaporin 2
medicine.diagnostic_test
Sodium-Hydrogen Exchanger 3
Chemistry
Osmolar Concentration
Biological Transport
Articles
Water-Electrolyte Balance
PPAR gamma
Plasma osmolality
Disease Models, Animal
medicine.anatomical_structure
Endocrinology
Thiazolidinediones
medicine.drug
Subjects
Details
- ISSN :
- 15221466 and 1931857X
- Volume :
- 305
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Renal Physiology
- Accession number :
- edsair.doi.dedup.....d2b7fa94ebb1e75d3190f82760f32820