C-peptide On The Impact Of The Intervention Effects And Mesangial Cell Matrix Synthesis And Degradation Of Rat Diabetic Nephropathy

PART ONE Prevention of Diabetic Nephropathy in STZ Induced Diabetic Rats Treated by C-peptideObjective: To investigate the prevention effects of C-peptide on morphological and functional changes of diabetic nephropathy under non-metabolic control in STZ induced diabetic rats, and to compare the effects with those of insulin.Methods: Three groups of STZ induced diabetic rats were included: diabetic rats with intensive blood glucose control by insulin (IG group); diabetic rats with constant high blood glucose level treated by C-peptide (130nmol/kg, sc, twice daily) (HG-C group); diabetic rats with high blood glucose level (HG group). Age matched normal rats served as controls (N group). 8 weeks or 12 weeks later, kidney weight was taken and ratio of kidney weight/body weight (KW/BW) was calculated. Glomerular volume V(glom) and extracellular matrix area fraction of glomerular cross-section S(ECM)/S(glom) were measured under light microscope with Color Image System on PAS stained kidney slices. Glomerular basement membrane thickness (GBMT) was measured under electronic microscope with Medical Image System. Urinary albumin excretion rate (UAER) was measured with ELISA method.Results: In 8 week experiment, V(glom) and S(ECM)/S(glom) of HG-Cgroup were about 50% and 31% smaller than those of HG group (P<0.001) and reached the level of IG group and N group. KW/BW and UAER of HG-C group were lower than HG group (P=0.03 and P=0.059 respectively), but still higher than IG group (P=0.001 and P=0.019 respectively). In 12 week experiment, V(glom) and S(ECM)/S(glom) of HG-C group were about 51% and 74% of those of HG group (P<0.001) and reached the level of IG group and N group. There was no statistical difference in GBMT among groups in both experiments.Conclusion: The accumulation of glomerular extracellular matrix which leads to mesangial expansion and glomerular hypertrophy can be completely prevented by C-peptide treatment independent of metabolic control in STZ rats, the target site of which may be the glomerular mesangial cell. However the prevention effects of C-peptide on the whole kidney hypertrophy and the leakage of urinary albumin is weaker than that of intensive blood glucose control by insulin treatment, and the discrepancy becomes more apparent with the prolonged course of diabetes. C-peptide combined with insulin treatment may help retard the development and progression of diabetic nephropathy.