In the present study, we tested the hypothesis whether creatine, a met
abolite of arginine metabolism, shares the pharmacological activities
of arginine reducing collagen accumulation in the diabetic kidney. Ten
db/db mice were given, for 3 months, a solution containing a daily do
sage of creatine of 50 mg/kg body weight. Eleven db/db mice served as
controls. At the end of the 3-month study period, the mean N-carboxyme
thyllysine concentration in the untreated group was significantly high
er than in the treated group (0.163 +/- 0.18 versus 0.096 +/- 0.017 nm
ol/mu mol hydroxyproline, p<0.001). Collagen accumulation was also sig
nificantly higher in the untreated than in the treated group (2.21 +/-
0.24 versus 1.68 +/- 0.22 mu mol hydroxyproline/100 mg kidney weight,
p < 0.001). We conclude that creatine led to a significant reduction
in collagen type IV accumulation resembling arginine or aminoguanidine
action. We do suggest that the guanidino group common to both compoun
ds is able to block reactive carbonyls.