Diabetic neuropathy in sucrose-fed Otsuka Long-Evans Tokushima fatty rats: effect of an aldose reductase inhibitor, TAT.
In an animal model of human non-insulin dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed with sucrose for 8 weeks to obtain severe hyperglycemia. The effects of sucrose administration on peripheral nerve functions, motor nerve conduction velocity (MNCV) and coefficient of variance of R-R interval (CVR-R), were investigated with concomitant measuring of sciatic nerve blood flow (SNBF), ADP-induced platelet aggregation and polyol content in the sciatic nerves. The effects of an aldose reductase inhibitor, TAT, on these parameters were also studied. Administration of sucrose to OLETF rats caused significant body weight reduction and remarkable hyperglycemia. Sucrose-fed OLETF rats demonstrated significantly delayed MNCV, decreased CVR-R, reduced SNBF and increased platelet aggregation activity to ADP. Sorbitol and fructose accumulation, and myo-inositol depletion in sciatic nerves were observed only in sucrose-fed OLETF rats. These abnormalities were all ameliorated by the treatment with TAT. These observations suggest that the sucrose-fed OLETF rat is a useful animal model for studying the pathogenesis of diabetic neuropathy in human NIDDM, and that an aldose reductase inhibitor is a useful therapeutic agent for the treatment of diabetic neuropathy.
Nakamura
J
J
The Third Department of Internal Medicine, Nagoya University School of Medicine, Showa-ku, Japan.
Koh
N
N
Sakakibara
F
F
Hamada
Y
Y
Wakao
T
T
Sasaki
H
H
Mori
K
K
Nakashima
E
E
Naruse
K
K
Hotta
N
N
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011108:Polymers / Q000378:metabolism; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000098:blood supply / Q000737:chemistry; D013395:Sucrose / Q000008:administration & dosage*; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D008055:Lipids; D010975:Platelet Aggregation Inhibitors; D011108:Polymers; D013777:Tetrazoles; D013876:Thiophenes; C024617:polyol; C080974:(5-(3-thienyl)tetrazol-1-yl)acetic acid; D013395:Sucrose; D000449:Aldehyde Reductase