Glucose-induced microvascular functional changes in nondiabetic rats are stereospecific and are prevented by an aldose reductase inhibitor.
Exposure of skin chamber granulation tissue vessels in nondiabetic rats to 11 or 15 mM D-glucose (but not L-glucose or 3-O-methylglucose) twice daily for 10 d induces vascular functional changes (increased albumin permeation and blood flow) identical to those in animals with mild or severe streptozotocin diabetes, respectively. These vascular changes are strongly linked to increased metabolism of glucose via the sorbitol pathway and are independent of nonenzymatic glycosylation as well as systemic metabolic and hormonal imbalances associated with the diabetic milieu. (J. Clin. Invest. 1990. 85:1167-1172.)
Williamson
J R
JR
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Ostrow
E
E
Eades
D
D
Chang
K
K
Allison
W
W
Kilo
C
C
Sherman
W R
WR
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003925:Diabetic Angiopathies / Q000209:etiology*; D005947:Glucose / Q000494:pharmacology*; D006031:Glycosylation; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism; D013237:Stereoisomerism; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D009281:Naphthalenes; D012709:Serum Albumin; C040550:tolrestat; D013012:Sorbitol; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D005947:Glucose