RT Journal Article
SR Electronic
T1 Polyol Pathway Hyperactivity Is Closely Related to Carnitine Deficiency in the Pathogenesis of Diabetic Neuropathy of Streptozotocin-Diabetic Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 897
OP 902
VO 287
IS 3
A1 Jiro Nakamura
A1 Naoki Koh
A1 Fumihiko Sakakibara
A1 Yoji Hamada
A1 Tomohiro Hara
A1 Hiromitsu Sasaki
A1 Sadao Chaya
A1 Taku Komori
A1 Eitaro Nakashima
A1 Keiko Naruse
A1 Koichi Kato
A1 Naohide Takeuchi
A1 Yasuhide Kasuya
A1 Nigishi Hotta
YR 1998
UL http://jpet.aspetjournals.org/content/287/3/897.abstract
AB To investigate the relationship between polyol pathway hyperactivity and altered carnitine metabolism in the pathogenesis of diabetic neuropathy, the effects of an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl]acetic acid (TAT), and a carnitine analog, acetyl-l-carnitine (ALC), on neural functions and biochemistry and hemodynamic factors were compared in streptozotocin-diabetic rats. Significantly delayed motor nerve conduction velocity, decreased R-R interval variation, reduced sciatic nerve blood flow and decreased erythrocyte 2,3-diphosphoglycerate concentrations in diabetic rats were all ameliorated by treatment with TAT (administered with rat chow containing 0.05% TAT, ∼50 mg/kg/day) or ALC (by gavage, 300 mg/kg/day) for 4 weeks. Platelet hyperaggregation activity in diabetic rats was diminished by TAT but not by ALC. TAT decreased sorbitol accumulation and prevented not onlymyo-inositol depletion but also free-carnitine deficiency in diabetic nerves. On the other hand, ALC also increased the myo-inositol as well as the free-carnitine content without affecting the sorbitol content. These observations suggest that there is a close relationship between increased polyol pathway activity and carnitine deficiency in the development of diabetic neuropathy and that an aldose reductase inhibitor, TAT, and a carnitine analog, ALC, have therapeutic potential for the treatment of diabetic neuropathy. The American Society for Pharmacology and Experimental Therapeutics