Additive Increase in Kidney Insulin-Like Growth Factor I and Initial Renal Enlargement in Uninephrectomized-Diabetic Rats

Summary

The initial renal hypertrophy in experimental diabetes and in response to uninephrectomy is associated with renal accumulation of insulin-like growth factor I (IGF-I). Since the combination of diabetes and nephrectomy almost doubles the initial renal growth rate the aim of the present study was to investigate the kidney IGF-I levels in the combined situation in uninephrectomized diabetic rats. Three experimental groups were exposed to either unilateral nephrectomy, streptozotocin-diabetes or both conditions and for four days animals from each group were taken out for investigation. After 4 days the wet kidney weight increased from baseline by 31% (from 661 ± 16 mg (SEM) to 866 ± 27 mg) (P < 0.01) in the uninephrectomized group, 32% (to 872 ± 18 mg) (P < 0.01) in the diabetic group and 46% (to 962 ± 27 mg) (P < 0.01) in the uninephrectomized-diabetic group. Kidney IGF-I concentrations were analyzed by radioimmunoassay and the increase from baseline on day 2 was 74% (from 262 ± 12 ng/g (SEM) to 456 ± 21 ng/g) (P < 0.01) in the uninephrectomized group, 58% (to 414 ± 18 ng/g) (P < 0.01) in the diabetic group and 176 ±% (to 722 ± 56 ng/g) (P < 0.01) in the combined group. Thereafter a decline in kidney IGF-I occurred in all groups, being normal at day 4 for the diabetic group, but still significantly higher in the uninephrectomized and uninephrectomized-diabetic groups compared to controls (P < 0.05%). These results demonstrate that the combination of uninephrectomy and diabetes induces an additive enhancement of kidney IGF-I accumulation and of the renal growth response compared to the isolated effect of the two conditions, giving further evidence for a causal role of IGF-I in diabetic and post-ne-phrectomy renal growth.

Key words

Hypertrophy - Insulin-Like Growth Factor I - Kidney - Rat - Streptozotocin Diabetes - Uninephrectomy