DIFFERENTIAL ACCUMULATION OF INSULIN-LIKE GROWTH-FACTOR-I IN KIDNEYS OF PREPUBERTAL AND POSTPUBERTAL STREPTOZOTOCIN-DIABETIC RATS

Nephropathy, one of the major complications of diabetes mellitus, is characterized by an early increase in kidney size. In experimental models of diabetes, this event is preceded by a rapid and transient rise in kidney IGF-I levels, at least in adult animals. Since diabetes-associated renal changes are uncommon in young patients, we investigated the early changes in the components of the IGF system following induction of diabetes in prepubertal and postpubertal rats. The rationale for this study was the evaluation of potential differences which could lead to kidney complications only at adult stages. Unlike the situation in the postpubertal kidney, in which there was a transient accumulation of extractable IGF-I 24-48 h after streptozotocin (STZ) administration, there was a decrease of similar to 12-fold in the level of IGF-I in the prepubertal kidney over the same period of time. Paradoxically, kidney IGF-I mRNA levels were reduced by similar to 50% in the postpubertal rat 24 h after STZ treatment, whereas in the prepubertal kidney IGF-I mRNA levels were unaltered. Furthermore, the levels of IGF-I receptor mRNA and I-125-labelled IGF-I binding to kidney membranes of postpubertal diabetic rats were similar to the levels in control kidneys. On the other hand, both the levels of IGF-I receptor mRNA and I-125-labelled IGF-I binding were increased (similar to 2.5-fold (after 24 h) and similar to 3-fold (after 48 h) respectively) in prepubertal animals. In addition, increased expression of IGF-binding protein (IGFBP)-1 mRNA was seen early in diabetes in both pre- and postpubertal rats. The results of this study suggest that the transient accumulation of IGF-I in the kidney of the postpubertal diabetic rat may not be due to an increase in the local synthesis of IGF-I, but rather to an increase in IGF-I uptake from the circulation due to non-membrane-associated IGFBP-1. The lack of accumulation of IGF-I in the prepubertal kidney probably reflects the similar to 10-fold lower levels of circulating IGF-I in young as compared with adult diabetic rats.