Connective tissue metabolism in diabetic peripheral nerves

Diabetes mellitus is associated with multiple connective tissue changes, such as generalized thickening of basement membranes. These alterations are suspected of contributing to the development of diabetic long-term complications encountered in many organs, including kidney, eye and peripheral nerves. The latter tissue, however, has gained relatively little attention with respect to connective tissue changes associated with diabetes. The morphological alterations of connective tissue in the diabetic peripheral nerve include thickening of basement membranes, increased diameter of endoneurial collagen fibrils, and accumulation of microfibrillar material. Recent studies have further elucidated the changes in the extracellular matrix of diabetic nerves and the molecular mechanisms underlying these alterations. For instance, elevated glucose concentrations modulate the expression of several proteins of the extracellular matrix in cultured nerve-derived connective tissue cells. In this article, we review the recent progress in the field of connective tissue alterations in diabetes and particularly in the diabetic peripheral nerve.