Effect of Diabetes and Insulin on Rat Renal Glomerular Protocollagen Hydroxylase Activities

The effect of diabetes and insulin on the activities of both prolyl hydroxylase (trivial name; proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) and lysyl hydroxylase (trivial name; lysine,2-oxoglutarate dioxygenase, EC 1.14.11.4) in isolated rat renal glomeruli was determined. Three groups of experimental animals were used: age-matched controls, streptozotocin-diabetic, and insulin-treated streptozotocin-diabetic. Using 14C-labeled lysine or proline hydroxylase substrate prepared from chick embryo tibiae, glomerular 17 000 X g supernatant enzyme was incubated in a complete hydroxylating system for 60 and 120 min Lysyl hydroxylase activity was significantly increased in diabetic preparations, but prolyl hydroxylase activity did not differ from control. Administration of insulin to streptozotocin-injected animals completely restored glomerular lysyl hydroxylase to normal levels. The results suggest that the specific elevation of lysyl hydroxylase relates to the biochemical changes contributory to diabetic nephropathy, and that insulin may reverse this process.