NDT Advance Access originally published online on January 21, 2005
Nephrology Dialysis Transplantation 2005 20(3):532-538; doi:10.1093/ndt/gfh683
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C-peptide prevents glomerular hypertrophy and mesangial matrix expansion in diabetic rats
1 Department of Nephrology, Danderyd Hospital, Departments of 2 Nephrology, 3 Pathology and 4 Clinical Physiology, Karolinska University Hospital, Stockholm and 5 Department of Cell Biology, Biomedicum, Uppsala University, Sweden
Correspondence and offprint requests to: Björn Samnegård, MD, Department of Nephrology, Danderyd Hospital, SE-182 88 Stockholm, Sweden. E-mail: bjorn.samnegard{at}medks.ki.se
Background. There is accumulating evidence that C-peptide exerts beneficial renal effects in type-1 diabetes by reducing glomerular hyperfiltration, albuminuria and glomerular hypertrophy in the early stage of nephropathy. The aim of this study was to clarify further the effects of C-peptide on renal structural changes in type-1 diabetic rats.
Methods. The effects of C-peptide or placebo on glomerular volume, mesangial expansion, glomerular basement membrane thickness, albuminuria and glomerular filtration rate (GFR) were studied in three groups of rats: a non-diabetic group (N, n = 9) and two groups that, during 8 weeks of diabetes, were left untreated for 4 weeks and then given a subcutaneous infusion of either placebo (D, n = 11) or C-peptide (DCp, n = 11) during the next 4 weeks. Furthermore, GFR was studied after 4 weeks of diabetes in an additional diabetic group (D-early, n = 9) and in an age-matched non-diabetic group (N-early, n = 9).
Results. After 4 weeks, GFR in the D-early group was 102% higher than in the N-early group. GFR after 8 weeks did not differ between the study groups. The D group presented with a 33% larger glomerular volume than the N group (P<0.001), while glomerular volume in the DCp group was similar to that in the N-group. Total mesangial and mesangial matrix fractions were increased by 46% (P<0.001) and 133% (P<0.001), respectively, in the D group. The corresponding values in the DCp group did not differ from those for the non-diabetic animals. Neither the thickness of the glomerular basement membrane nor the level of albuminuria differed significantly between the study groups.
Conclusions. C-peptide administration in replacement dose to streptozotocin-diabetic rats serves to limit or prevent the glomerular hypertrophy and the mesangial matrix expansion seen in the post-hyperfiltration phase of early diabetic nephropathy.
Keywords: C-peptide; diabetic nephropathy; glomerular basement membrane thickness; glomerular hypertrophy; glomerular hyperfiltration; mesangial expansion
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