Increased Urinary Excretion of Pyridinium Crosslinks in Streptozotocin-induced Diabetic Rats

We assessed the changes in the urinary excretions of bone breakdown markers, i.e. two pyridinium crosslinks, pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), and two hydroxylysine glycosides, glucosylgalactosylhydroxylysine (GGH) and galactosylhydroxylysine (GH), in streptozotocin (STZ)-induced diabetic rats. The 24-h urinary excretions of the crosslinks in diabetic rats increased in a biphasic manner after STZ-injection. The first peak appeared during the day after the STZ-injection, i.e., 53% higher than control for Pyr and 62% higher for D-Pyr and the second peak appeared during the second week after the STZ-injection, being 56% higher for Pyr and 81% higher for D-Pyr. The urinary excretions of glycosides, however, were almost the same level as those of the control throughout the experimental period (6 weeks). In normal rats, the ratio of the crosslinks to the glycosides in urine was found to be lower than that in serum. This suggests that the selective reabsorption of the crosslinks occurs in the rat kidney. The apparent increased urinary excretion of pyridinolines in diabetic rats might be ascribed to the disorder of the renal reabsorption.