REDUCTION OF ADVANCED GLYCATION END-PRODUCT (AGE) LEVELS IN NERVOUS-TISSUE PROTEINS OF DIABETIC LEWIS RATS FOLLOWING ISLET TRANSPLANTS IS RELATED TO DIFFERENT DURATIONS OF POOR METABOLIC CONTROL

Advanced glycation end-products (AGEs) are irreversible compounds whic h, by abnormally accumulating over proteins as a consequence of diabet ic hyperglycaemia, can damage tissues and thus contribute to the patho genesis of diabetic complications. This study was performed to evaluat e whether restoration of euglycaemia by islet transplantation modifies AGE accumulation in central and peripheral nervous tissue proteins an d, as a comparison, in proteins from a non-nervous tissue. Two groups of streptozotocin diabetic inbred Lewis rats with 4 (T1) or 8 (T2) mon ths disease duration were grafted into the liver via the portal vein w ith 1200-1500 islets freshly isolated from normal Lewis rats. Transpla nted rats, age-matched control and diabetic rats studied in parallel, were followed for a further 4-month period. At study conclusion, glyca emia, glycated haemoglobin and body weight were measured in all animal s, and an oral glucose tolerance test (OGTT) performed in transplanted rats. AGE levels in cerebral cortex, spinal cord, sciatic nerve prote ins and tail tendon collagen were measured by enzyme-linked immunosorb ent assay (ELISA). Transplanted animal OGTTs were within normal limits , as were glycaemia and glycated haemoglobin. Diabetic animal AGEs wer e significantly higher than those of control animals. Protein AGE valu es were reduced in many transplanted animals compared to diabetic anim als, reaching statistical significance in spinal cord (P < 0.05), scia tic nerve (P < 0.02) and tail tendon collagen (P < 0.05) of T1 animals . Thus, return to euglycaemia following islet transplantation after 4 months of diabetes with poor metabolic control reduces AGE accumulatio n rate in the protein fractions of the mixed and purely peripheral ner vous tissues (spinal cord and sciatic nerve, respectively). However, a fter a double duration of bad metabolic control, a statistically signi ficant AGE reduction has not been achieved in any of the tissues, sugg esting the importance of an early therapeutic intervention to prevent the possibly pathological accumulation of AGEs in nervous and other pr oteins.