Effect of metformin on advanced glycation endproduct formation and peripheral nerve function in streptozotocin-induced diabetic rats.
The effects of metformin treatment on advanced glycation endproduct formation and peripheral nerve function in streptozotocin-induced diabetic rats were examined. Streptozotocin-induced diabetic rats were treated with low dose metformin (50-65 mg kg(-1) daily) or high dose metformin (500-650 mg kg(-1) daily) for 10 weeks. While the metformin-untreated diabetic group showed a significant increase of advanced glycation endproducts (6.1-fold in the lens, 1.6-fold in the sciatic nerve, 2.3-fold in the renal cortex, and 1.9-fold in plasma; all P < 0.01) compared with the healthy control group, both metformin-treated groups had significantly less advanced glycation endproduct deposition. The % decrease in the diabetes-induced increase in advanced glycation endproduct formation by low and high dose metformin treatment was 25% and 72% in the lens (both P < 0.01), 31% and 42% in the sciatic nerve (both P < 0.05), and 16% and 33% in the renal cortex (P < 0.05 and P < 0.01), respectively. However, the plasma advanced glycation endproduct level showed no significant difference from that in the untreated diabetic group, in spite of slight decrease in plasma glucose and glycated hemoglobin levels in the metformin-treated groups. The diabetes-induced sciatic nerve conduction velocity deficits were improved by 46% and 42% by low and high dose metformin treatment, respectively (both P < 0.01). These data suggest that metformin may have a direct antiglycative action, which in turn contributes to amelioration of peripheral nerve function. Thus, metformin treatment may be effective in the prevention of diabetic complications through not only lowering plasma glucose, but also directly inhibiting advanced glycation endproduct formation.
Tanaka
Y
Y
Department of Medicine, Metabolism and Endocrinology, School of Medicine, Juntendo University, Tokyo, Japan.
Uchino
H
H
Shimizu
T
T
Yoshii
H
H
Niwa
M
M
Ohmura
C
C
Mitsuhashi
N
N
Onuma
T
T
Kawamori
R
R
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000096:biosynthesis* / Q000097:blood; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007672:Kidney Cortex / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D009431:Neural Conduction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D008687:Metformin