Decrease in the glycosaminoglycan content in the skin of diabetic rats. The role of IGF-I, IGF-binding proteins and proteolytic activity.

The results of our previous studies demonstrated that acute streptozotocin-induced diabetes in rats evoked a decrease in skin collagen content with little effect on glycosaminoglycans (GAG) content. In our present study we employed the model of chronic diabetes in order to check its effect on skin GAG content. It was found that the skin of diabetic rats showed a significant decrease in almost all the investigated GAGs by 50-70%. The decrease in heparan sulfate content was slight and statistically insignificant. We sought to determine whether the insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGF-BPs) levels are altered in animals with experimental diabetes and might contribute to the decrease in tissue GAG content. Circulating IGF-I level was found to be reduced in animals with diabetes and significant changes in serum IGF-BPs were observed. The amount of high molecular weight binding proteins (HMW-BPs) was decreased and the content of low molecular weight binding proteins (LMW-BPs), known as IGF-I inactivating substances, markedly increased. Furthermore, diabetic rats demonstrated an increase of skin proteolytic activity. We conclude that the decrease of GAG content in the skin of diabetic rats is a result of three co-existing phenomena: decreased circulating IGF-I level, increased plasma content of LMW-BPs and increased proteolytic activity of the skin.