C-peptide prevents glomerular hypertrophy and mesangial matrix expansion in diabetic rats.
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.
Samnegård
Björn
B
Department of Nephrology, Danderyd Hospital, SE-182 88 Stockholm, Sweden. bjorn.samnegard@medks.ki.se
Jacobson
Stefan H
SH
Jaremko
Georg
G
Johansson
Bo-Lennart
BL
Ekberg
Karin
K
Isaksson
Britta
B
Eriksson
Linda
L
Wahren
John
J
Sjöquist
Mats
M
D000419:Albuminuria / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology; D002096:C-Peptide / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology* / Q000503:physiopathology*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D002096:C-Peptide; D013311:Streptozocin