Changes in IGF-binding proteins in rats with experimental diabetes.

The effects of streptozotocin-induced diabetes on proteolytic activity and collagen biosynthesis in skin lesions in rats and on IGF-I binding proteins in their serum were evaluated. It was found that both collagen in intact skin and collagen biosynthesis in skin lesions were lower compared to control animals. Concurrently, there was an increase in proteolytic activity both in intact and lesioned skin. The livers and sera of diabetic animals also showed higher proteolytic activity. Inhibitors of cathepsin D (pepstatin and potato-derived inhibitor) prevent the decrease of collagen biosynthesis in the skin of diabetic rats. These observations indicate the co-existence of two phenomena in the investigated animals: an increase in proteolytic activity in tissues and a decrease in collagen biosynthesis. Furthermore, the diabetic rats showed significant changes in the composition of IGF-I serum binding proteins. The amount of high molecular weight binding proteins (HMW-BPs) was distinctly decreased, whereas the content of low molecular weight binding proteins (LMW-BPs) was significantly increased. Large amounts of LMW-BPs have been previously found in the sera of fasted and scorbutic animals. They are inhibitors of IGF-I activity. It is suggested that the increase in LMW-BP concentration in diabetic serum may be responsible for the inactivation of IGF-I resulting in decreased collagen biosynthesis. The role of proteolysis in the production of LMW-BPs in diabetic serum is discussed.