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 c haracterized by an early increase in kidney size. In experimental mode ls of diabetes, this event is preceded by a rapid and transient rise i n kidney IGF-I levels, at least in adult animals. Since diabetes-assoc iated renal changes are uncommon in young patients, we investigated th e early changes in the components of the IGF system following inductio n of diabetes in prepubertal and postpubertal rats. The rationale for this study was the evaluation of potential differences which could lea d to kidney complications only at adult stages. Unlike the situation i n the postpubertal kidney, in which there was a transient accumulation of extractable IGF-I 24-48 h after streptozotocin (STZ) administratio n, 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, k idney IGF-I mRNA levels were reduced by similar to 50% in the postpube rtal rat 24 h after STZ treatment, whereas in the prepubertal kidney I GF-I mRNA levels were unaltered. Furthermore, the levels of IGF-I rece ptor mRNA and I-125-labelled IGF-I binding to kidney membranes of post pubertal 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-la belled IGF-I binding were increased (similar to 2.5-fold (after 24 h) and similar to 3-fold (after 48 h) respectively) in prepubertal animal s. In addition, increased expression of IGF-binding protein (IGFBP)-1 mRNA was seen early in diabetes in both pre- and postpubertal rats. Th e 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 i n IGF-I uptake from the circulation due to non-membrane-associated IGF BP-1. The lack of accumulation of IGF-I in the prepubertal kidney prob ably reflects the similar to 10-fold lower levels of circulating IGF-I in young as compared with adult diabetic rats.