| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 19, 2006
Accepted on July 28, 2006
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115
* To whom correspondence should be addressed. E-mail: gadler{at}partners.org.
To determine whether mineralocorticoid receptor (MR) activation plays a role in diabetic renal injury and whether this role differs in type 1 and type 2 diabetes mellitus, we examined the effect of a MR antagonist on renal injury in rodent models of type 1 (streptozotocin treated rat) and type 2 (db/db mouse) diabetes. We studied 3 groups of 8 week-old, uninephrectomized Wistar rats for 4 weeks: diabetic streptozotocin (55 mg/kg) treated rats (n = 11), diabetic streptozotocin treated rats receiving the MR antagonist eplerenone (n = 15) and non-diabetic rats (n = 9). In addition, we studied 3 groups of 8 week-old mice for 16 weeks: diabetic db/db mice (n = 10), diabetic db/db mice treated with eplerenone (n = 8) and non-diabetic, db/+ littermates (n = 11). Diabetic rats and mice developed albuminuria and histopathological evidence of renal injury, including glomerular hypertrophy, mesangial expansion and tubulointerstitial injury, as well as increased renal cortical levels of MR protein, MR mRNA, transforming growth factor 
mRNA and osteopontin mRNA. All of these changes were significantly reduced by treatment with eplerenone except for the elevated MR levels. The beneficial effects of eplerenone were not attributable to changes in blood pressure or glycemia. In summary, MR expression was increased in kidneys of diabetic rodents, and MR antagonists effectively reduced diabetic renal injury irrespective of the species or the specific cause of the diabetes. Thus, these data suggest that MR activation is a critical factor in the early pathogenesis of renal disease in both type 1 and type 2 diabetes mellitus.
This article has been cited by other articles:
 |
|
 |
|
  J. Su, P. A. Lucchesi, R. A. Gonzalez-Villalobos, D. I. Palen, B. M. Rezk, Y. Suzuki, H. A. Boulares, and K. Matrougui Role of Advanced Glycation End Products With Oxidative Stress in Resistance Artery Dysfunction in Type 2 Diabetic Mice Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1432 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Belmadani, D. I. Palen, R. A. Gonzalez-Villalobos, H. A. Boulares, and K. Matrougui Elevated Epidermal Growth Factor Receptor Phosphorylation Induces Resistance Artery Dysfunction in Diabetic db/db Mice Diabetes, June 1, 2008; 57(6): 1629 - 1637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. W. Krug and M. Ehrhart-Bornstein Aldosterone and Metabolic Syndrome: Is Increased Aldosterone in Metabolic Syndrome Patients an Additional Risk Factor? Hypertension, May 1, 2008; 51(5): 1252 - 1258. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Guo, V. Ricchiuti, B. Q. Lian, T. M. Yao, P. Coutinho, J. R. Romero, J. Li, G. H. Williams, and G. K. Adler Mineralocorticoid Receptor Blockade Reverses Obesity-Related Changes in Expression of Adiponectin, Peroxisome Proliferator-Activated Receptor-{gamma}, and Proinflammatory Adipokines Circulation, April 29, 2008; 117(17): 2253 - 2261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. C. Connell, S. M. MacKenzie, E. M. Freel, R. Fraser, and E. Davies A Lifetime of Aldosterone Excess: Long-Term Consequences of Altered Regulation of Aldosterone Production for Cardiovascular Function Endocr. Rev., April 1, 2008; 29(2): 133 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brown Aldosterone and Vascular Inflammation Hypertension, February 1, 2008; 51(2): 161 - 167. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
