Advanced glycosylation end products, protein kinase C and renal alterations in diabetic rats.
OBJECTIVE
To study the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on renal alteration in diabetic rats.


METHODS
Insulin or aminoguanidine was administered to diabetic rats. Blood glucose, hemoglobin A1c (HbA1c), glomerular tissue extracts AGE (GTE-AGE), PKC, glomerular basement membrane thickness (GBMT) and urine protein/creatinine (Pr/Cr) ratio in diabetic rats were measured and analysed.


RESULTS
Levels of blood glucose, HbA1c and AGE, PKC activity, the Pr/Cr ratio and GBMT were all significantly increased (P values all less than 0.01) in diabetic rats. Insulin could decrease the formation of HbA1c 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 delay the increase of urine Pr/Cr ratio and GBMT (P < 0.05 or P < 0.01).


CONCLUSIONS
Chronic hyperglycemia may lead to an increase of PKC activity. HbA1c and AGE may not directly contribute to alterations of PKC activity, but the increase of PKC activity could promote the action of AGE on GBM thickening. It is important to inhibit the formation of AGE and reduce the PKC activity so as to prevent or delay the development of diabetic nephropathy.
Rong
J
J
Department of Endocrinology, Daping Hospital of Third Military Medical University, Chongquing 400042, China. rongjan@public.cta.cq.cn
Qiu
H
H
Wang
S
S
D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D003404:Creatinine; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D006146:Guanidines; D007328:Insulin; D011493:Protein Kinase C; C004479:pimagedine