Alterations in glycosaminoglycans in wounded skin of diabetic rats. A possible role of IGF-I, IGF-binding proteins and proteolytic activity.

In the skin of diabetic animal tissues the amount of extracellular matrix (ECM) components is drastically decreased as a result of a reduced rate of their biosynthesis or increased degradation. In the present study we have investigated the mechanism of poor wound healing in diabetic rats. We have found that wounded skin of diabetic rats shows a significant decrease in glycosaminoglycan (GAG) content compared to that of control animals. This decrease was accompanied by significant depletion of insulin-like growth factor-I (IGF-I), known as a stimulator of GAG biosynthesis, and a distinct decrease in the content of high molecular weight IGF-binding proteins (HMW-BPs) with a simultaneous increase in low molecular weight IGF-binding proteins (LMW-BPs) in the sera of diabetic animals. Basing on determination of proteolytic activities we suggest that insulin shortage in diabetes results in increased proteolytic activity in various tissues. Proteolytic enzymes may cleave the HMW-BPs and convert them to LMW-BPs. The LMW-BPs may inactivate IGF-I and eliminate its stimulatory effects on GAG biosynthesis. The proteolytic enzymes may also digest the protein cores of proteoglycans releasing the GAGs and making them more susceptible to the action of glycosidases. These phenomena may be responsible for the observed marked decrease in GAG content in the skin of diabetic rats and disturb the wound-healing process.