Advanced glycation end product levels in eye lenses, aorta, and tail tendon in transplanted diabetic inbred Lewis rats

Background. Pancreatic islet transplantation in diabetes, by restoring eugl ycemia, should in time correct the abnormal accumulation of advanced glycat ion end products (AGEs) over target tissues, thus delaying the development of late diabetic complications. Methods. Homologous islet transplantation was performed in inbred Lewis rat s 15 days (TA), 4 months (TB), and 8 months (TC) after streptozotocin diabe tes. Group TA was studied for 12 months and groups TB and TC were studied f or 4 months after transplantation. Normal (N) and diabetic (D) rats formed the control groups. Metabolic control in the transplant (T) groups was eval uated by oral glucose tolerance test. Blood glucose, glycated hemoglobin, a nd body weight were determined in all groups. AGE levels were determined by spectrofluorometry in eye lens proteins and by ELISA in aortic and tail te ndon collagen. Results. T groups showed normal oral glucose tolerance tests and metabolic parameters. The latter were altered in all D groups (P <0.005 to P <0.0001 versus N and T groups). AGEs were increased in the D groups (P <0.05 to P < 0.001) versus the N groups. AGEs in the TA and TB groups were not different from those of the N groups but were significantly reduced (P <0.05 to P <0 .001) when compared with those of the D groups. In the TC group, eye lens A GEs were significantly elevated (P <0.001) or significantly reduced (P <0.0 1) when compared with those of the N or D groups, respectively. Aortic coll agen AGEs were elevated (P <0.01) by comparison with those of the N groups and not statistically different from those of the D groups. Tail tendon col lagen AGE levels lay between those of the N and D groups, without reaching a statistical significance. Conclusions. These results indicate that primary and early secondary (group s TA and TB) but not late secondary (group TC) islet transplantations are c apable of blocking or reducing an abnormal accumulation of AGEs, thus confi rming the importance of preventive transplantation therapies.