TRANSIENT INCREASE IN RENAL INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS DURING INITIAL KIDNEY HYPERTROPHY IN EXPERIMENTAL DIABETES IN RATS

The insulin-like growth factors, insulin-like growth factor I and insulin-like growth factor II are bound to six distinct classes of insulin-like growth factor binding proteins (IGFBPs) in the circulation and in extracellular fluids. Diabetic renal hypertrophy is preceded by a transient increase in kidney insulin-like growth factor I suggestive of a renotropic function for insulin-like growth factor I. In order to examine a possible involvement of IGFBPs in initial diabetic kidney growth and in kidney insulin-like growth factor I accumulation, we studied rat kidney IGFBPs by ligand blotting during the first 4 days after induction of diabetes. Six distinct bands were identified in kidney and liver tissue with apparent molecular weight values of 38-47 (doublet), 34,30, 24 and 20 kDa. The 38-47 kDa doublet band probably corresponds to the insulin-like growth factor binding subunit of IGFBP-3, the 24 kDa band to IGFBP-4 and the 30 kDa band to IGFBP-1 and/or IGFBP-2, as these IGFBPs in rats have similar molecular weight. In untreated diabetic rats a transient increase in the kidney 30 kDa band was demonstrable 24 h after induction of diabetes with a maximal rise (two-fold) after 48 h, followed by a decrease to baseline values after 4 days. In untreated diabetic rats the 38-47 kDa doublet band also increased (two-fold) in kidney during the first 2 days after induction of diabetes, followed by a subsequent decrease. Insulin-treatment prevented both thc increase in the 30 kDa and in the 38-47 kDa bands. Kidney weight in untreated diabetic rats increased by 26% after 4 days. In conclusion, the present study shows a transient increase in the 30 kDa and the 38-47 kDa IGFBP species in hypertrophying diabetic kidneys, contemporarily with the previously described transient increase in extractable kidney insulin-like growth factor I content. These findings support the concept that IGFBPs may be involved in the action of insulin-like growth factor I and possibly in the diabetic kidney insulin-like growth factor I accumulation.