Vascular filtration function in galactose-fed versus diabetic rats: the role of polyol pathway activity.
These studies were undertaken to assess the effects of increased galactose (v increased glucose) metabolism via the polyol pathway on vascular filtration function in the kidneys, eyes, nerves, and aorta. Quantitative radiolabeled tracer techniques were used to assess glomerular filtration rate (GFR) and regional tissue vascular clearance of plasma 131I-bovine serum albumin (BSA) in five groups of male Sprague-Dawley rats: nondiabetic controls, streptozotocin-diabetic rats, nondiabetic rats fed a 50% galactose diet, diabetic rats treated with sorbinil (an aldose reductase inhibitor), and galactose-fed rats treated with sorbinil. Sorbinil was added to the diet to provide a daily dose of approximately .2 mmol/kg body weight. After 2 months of diabetes or galactose ingestion, albumin clearance was increased twofold to fourfold in the eye (anterior uvea, choroid, and retina), sciatic nerve, aorta, and kidney; GFR was increased approximately twofold and urinary excretion of endogenous albumin and IgG were increased approximately 10-fold. Sorbinil treatment markedly reduced or completely prevented all of these changes in galactose-fed, as well as in diabetic rats. These observations support the hypothesis that increased metabolism of glucose via the sorbitol pathway is of central importance in mediating virtually all of the early changes in vascular filtration function associated with diabetes in the kidney, as well as in the eyes, nerves, and aorta. On the other hand, renal hypertrophy in diabetic rats and polyuria, hyperphagia, and impaired weight gain in galactose-fed and in diabetic rats were unaffected by sorbinil and therefore are unlikely to be mediated by increased polyol metabolism.
Pugliese
G
G
Department of Pathology, Washington University School of Medicine, St Louis, MO 63110.
Tilton
R G
RG
Speedy
A
A
Chang
K
K
Province
M A
MA
Kilo
C
C
Williamson
J R
JR
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001808:Blood Vessels / Q000503:physiopathology*; D003037:Cobalt Radioisotopes; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004492:Edetic Acid / Q000378:metabolism; D005123:Eye / Q000378:metabolism; D005690:Galactose / Q000494:pharmacology*; D005693:Galactosemias / Q000503:physiopathology; D005919:Glomerular Filtration Rate; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007074:Immunoglobulin G / Q000652:urine; D007457:Iodine Radioisotopes; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate; D011108:Polymers / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000098:blood supply / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism / Q000652:urine
D003037:Cobalt Radioisotopes; D007093:Imidazoles; D048289:Imidazolidines; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D011108:Polymers; C024617:polyol; D012710:Serum Albumin, Bovine; D004492:Edetic Acid; C026411:sorbinil; D005690:Galactose