Slowing of peripheral motor nerve conduction was ameliorated by aminoguanidine in streptozocin-induced diabetic rats.
The aims of this study were to investigate the effect of aminoguanidine (AG) on slowing of motor nerve conduction velocity (MNCV) of the sciatic nerve in streptozocin-induced diabetic rats and to assess its mechanism of action. The MNCV of the sciatic nerve was measured electrophysiologically in diabetic rats treated with and without AG for 16 weeks. To elucidate the action of AG, morphological lesion and abnormality of polyol pathway metabolism in the nerve were examined and tissue levels of advanced glycosylation end-products (AGE) were determined as an indicator of AGE accumulation in tissue. Diabetic rats were treated with AG at three doses of 10, 25 and 50 mg/kg for 16 weeks. Myelinated fiber morphometry and nerve Na+,K(-)-ATPase activity were determined. The AGE levels in renal cortex were measured by a specific ELISA. Aminoguanidine dose-dependently ameliorated slowing of MNCV 16 weeks after the treatment without changing body weight or blood glucose levels. No difference in myelinated fiber morphometry or Na+,K(+)-ATPase activity with or without AG treatment was detected in diabetic rats. Diabetes increased the AGE level in the renal cortex by six times compared to non-diabetic rats, and AG reduced the rise in the AGE level by 40%. The MNCV was inversely correlated with the AGE levels. We conclude that improvement of conduction slowing by AG in experimental diabetes may be through decreasing the AGE level in the peripheral tissues. Aminoguanidine may have a therapeutic potential in controlling diabetic peripheral neuropathy.
Miyauchi
Y
Y
Endocrinology and Metabolic Disease Research Laboratory, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Japan.
Shikama
H
H
Takasu
T
T
Okamiya
H
H
Umeda
M
M
Hirasaki
E
E
Ohhata
I
I
Nakayama
H
H
Nakagawa
S
S
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D019270:Fructosamine; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D006595:Hexosamines / Q000097:blood; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009046:Motor Neurons / Q000502:physiology*; D009431:Neural Conduction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D001786:Blood Glucose; D006146:Guanidines; D006595:Hexosamines; D019270:Fructosamine; D000254:Sodium-Potassium-Exchanging ATPase; C004479:pimagedine