NONENZYMATIC GLYCATION OF PERIPHERAL AND CENTRAL-NERVOUS-SYSTEM PROTEINS IN EXPERIMENTAL DIABETES-MELLITUS

Nonenzymatic glycation of neural proteins could underlie diabetic peri pheral neuropathy. Cytoskeletal and myelin protein fractions of centra l nervous system and peripheral nervous system (PNS) tissue from rats with streptozotocin-induced diabetes of 1.5 and 8 months duration were analyzed for glycation products. In sciatic nerve cytoskeletal prepar ations from both diabetic and control animals we found high levels of the early glycation product (measured as furosine) after 6 weeks, whic h had fallen markedly by 8 months. Conversely the advanced glycation e nd product (AGE), pentosidine, was low at 6 weeks and high by 8 months in diabetic animals. The levels of glycation products were much lower in spinal cord and spinal nerve from diabetic animals. There was incr eased borotritride labeling of neurofilament subunits, and of cross-li nked material, in cytoskeletal fractions of diabetic sciatic nerves. T hese results show that the PNS cytoskeleton is vulnerable to nonenzyma tic glycation, resulting in AGE formation, in diabetic rats and to a l esser extent in normals. (C) 1997 John Wiley & Sons, Inc.