Increased ornithine decarboxylase activity in kidneys undergoing hypertrophy in experimental diabetes

Abstract

Renal hypertrophy and hyperfiltration are early manifestations of human and experimental diabetes that may contribute to the late development of diabetic nephropathy. The biochemical events resulting in kidney growth in the diabetic state are completely unknown. Since growth of various tissues is accompanied by increased formation of polyamines, we studied whether polyamines were involved in the growth of the kidney observed in diabetic rats. This was done by measuring the activity of the rate-limiting enzyme in the polyamine pathway (ornithine decarboxylase; ODC) in kidneys from control, diabetic and insulin-treated diabetic animals. The ODC activity in the kidney was increased in the diabetic animals with a maximal rise 24 h after diabetes induction (6-fold, P< 0.01); the activity thereafter declined. However, on day 14 the activity was still significantly elevated (2.5-fold, P< 0.05). In insulin-treated diabetic animals the kidney ODC activity was only increased 3-fold ( P< 0.05) after 24 h, and for the rest of the study period the activity was about 1.8-fold higher than in control rats. After 14 days the kidneys from diabetic rats were significantly larger than kidneys from both control and insulin-treated diabetic rats, 1066 ± 43 mg vs. 904 ± 16 mg and 959 ± 36 mg, respectively ( P< 0.01). For comparison, the ODC activity was also investigated in muscle. However, in muscle from diabetic animals the ODC activity declined steadily during the 14 days to 34% of control values ( P< 0.01), and insulin treatment completely normalized the ODC activity in muscle. Our findings demonstrate for the first time an early increase in kidney ODC activity preceding renal hypertrophy in experimental diabetes. Furthermore, insulin treatment of diabetic rats reduced the diabetes-induced increase in ODC activity and prevented the kidney growth associated with diabetes. These findings support the idea that polyamines may be involved in diabetic renal hypertrophy.