Glomerular basement membrane thickening in streptozotocin diabetic rats despite treatment with an aldose reductase inhibitor.
This study concerns the possible prevention of glomerular basement membrane thickening in experimental diabetes by an aldose reductase inhibitor (ARI), Statil. ARI added to the chow was given to streptozotocin diabetic rats over a period of 6 months. Reference groups were control rats and diabetic rats on the same chow without ARI. The diabetic rats were given insulin two or three times a week, and blood glucose was measured monthly before insulin injections. There was a marked difference in the occurrence of cataracts between the two diabetic groups. ARI treated rats tended to have lower blood glucose than the diabetic reference group, but the difference was not significant. At the termination of the experiment, the left kidney was perfusion fixed, weighed, and prepared for light and electron microscopy. Systematic random sampling from the entire kidney was performed to obtain light microscopic visual fields and ultrathin sections from two glomeruli. Mean glomerular volume was estimated by light microscopy, and glomerular basement membrane thickness, by electron microscopy. Basement membrane thickness was significantly increased in untreated diabetic rats (174 nm, SD = 4.5 nm) as compared to that of controls (Mean: 154 nm, SD = 11.0 nm), and was even more so in ARI treated rats (187 nm, SD = 18.7 nm), although the ARI treated rats showed less renal and glomerular hypertrophy than did untreated diabetic rats. In conclusion, the ARI treatment over an experimental period of 6 months attenuated diabetic renal and glomerular hypertrophy, but had no effect at all on diabetic glomerular basement membrane thickening.
Osterby
R
R
Electron Microscopic Diabetes Research Laboratory, Aarhus University, Denmark.
Gundersen
H J
HJ
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D010793:Phthalazines / Q000627:therapeutic use*; D011724:Pyridazines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D001786:Blood Glucose; D010793:Phthalazines; D011724:Pyridazines; C042829:ponalrestat; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase