Advanced glycosylation end products, protein kinase C and renal alterations in diabetic rats

Objective To study the relationship between advanced glycosylation end prod ucts (AGE) and protein kinase C (PKC), and their effects on renal alteratio n in diabetic rats. Methods Insulin or aminoguanidine was administered to diabetic rats. Blood glucose, hemoglobin A(1C) (HbA(1C)), glomerular tissue extracts AGE (GTE-AG E), PKC, glomerular basement membrane thickness (GBMT) and urine protein/cr eatinine (Pr/Cr) ratio in diabetic rats were measured and analysed. Results Levels of blood glucose, HbA(1C) and AGE, PKC activity, the Pr/Cr r atio and GBMT were all significantly increased (P values all less than 0.01 ) in diabetic rats. Insulin could decrease the formation of HbA(1C) and AGE , and improve PKC activity. Aminoguanidine had no influence on PKC activity (P > 0.05) although it decreased the formation of AGE. Both drugs could de lay the increase of urine Pr/Cr ratio and GBMT (P < 0.05 or P < 0.01). Conclusions Chronic hyperglycemia may Bead to an increase of PKC activity. HbA(1C) and AGE may not directly contribute to alterations of PKC activity, but the increase of PKC activity could promote the action of AGE on GEM th ickening. It is important to inhibit the formation of AGE and reduce the PK C activity so as to prevent or delay the development of diabetic nephropath y.