Original Paper

Diminished Proteinuria in Diabetes mellitus by Sorbinil, an Aldose Reductase Inhibitor
A. Beyer-Mears, E. Cruz, T. Edelist, E. Varagiannis

Departments of Physiology and Ophthalmology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, N.J., USA

Address of Corresponding Author

Pharmacology 1986;32:52-60 (DOI: 10.1159/000138152)

  Key Words

• Diabetes mellitus
• Sorbinil
• Aldose reductase inhibitor
• Proteinuria

  Abstract

Proteinuria was diminished by concomitant oral administration of sorbinil, an aldose reductase inhibitor to streptozotocin-induced diabetic rats. Animals were placed in one of three groups: control, diabetic, sorbinil-treated diabetic. For a period of 10 weeks, 24-hour urine samples were analyzed weekly for volume, glucose, ketone, total protein (Pesce-Strande) and individual protein components having molecular weights between 15,000 and 120,000 daltons. The latter were examined by polyacrylamide gel electrophoresis and quantitated by laser densitometric analysis. Results indicated that controls excreted albumin (68,000 daltons) and low-molecular weight proteins between 15,000 and 20,000 daltons. Throughout the 10-week period of diabetes, there was a 7- to 12-fold increase in total urinary protein excreted in 24 h. Diabetic-induced proteinuria primarily resulted from excretion of newly detected proteins having molecular weights of 30,000-100,000 daltons and an increase amount of albumin. Sorbinil treatment prevented approximately 70% of the increase in total protein excretion despite persistent hyperglycemia, glycosuria and ketonuria. Laser densitometric analysis indicated that the aldose reductase inhibitor decreased by 70% the excretion of newly detected proteins and albumin while maintaining the 15,000- to 20,000-dalton proteins. These results suggest that the polyol pathway is implicated in diabetic-induced proteinuria and inhibition of aldose reductase may represent a therapeutic approach for management of diabetic nephropathy.

Copyright © 1986 S. Karger AG, Basel

  Author Contacts

Dr. Annette Beyer-Mears, Department of Physiology, H649, UMDNJ-New Jersey Medical, 100 Bergen Street Newark, NJ 07103 (USA)

  Article Information

Received: May 29, 1985
Accepted: July 8, 1985
Published online: June 04, 2008
Number of Print Pages : 9