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.

C-peptide and captopril are equally effective in lowering glomerular hyperfiltration in diabetic rats.

BACKGROUND: C-peptide has been shown to reduce glomerular hyperfiltration, glomerular hypertrophy and urinary albumin excretion in type 1 diabetes, but its effect has not been compared with that of an angiotensin-converting enzyme inhibitor (ACEI) in the early stage of renal involvement in diabetes. METHODS: Glomerular filtration rate (GFR) was measured in terms of inulin clearance and renal blood flow, using ultrasound technique, in four groups of streptozotocin-induced diabetic rats before and after a 60 min infusion of C-peptide (D-Cp), captopril (D-ACEI), C-peptide and captopril (D-Cp-ACEI) or placebo (D-placebo). In addition, a non-diabetic control group was studied before and after captopril infusion (C-ACEI). RESULTS: GFR was 37-51% higher in the diabetic groups than in the control animals. GFR decreased after treatment in the D-Cp, D-ACEI and D-Cp-ACEI groups, but did not change in the D-placebo group. Blood flow increased by 26-32% in the three groups receiving captopril and by 5% in the diabetic groups treated with C-peptide alone or placebo. The increase in blood flow in the three ACEI-treated groups was significantly greater than in the D-placebo group. Filtration fraction fell significantly in all groups, but only in the combined D-Cp-ACEI group did it fall significantly more than in the D-placebo group. CONCLUSIONS: C-peptide and captopril lower diabetes-induced glomerular hyperfiltration to a similar extent, but the influence of captopril on blood flow is greater than that of C-peptide, suggesting different mechanisms of action. No statistically significant additive effects of C-peptide and captopril were shown in this acute infusion study.