C-peptide Effects on Glomerular Filtration

In our previous visualisation study, we reported that there is a leakage of proteins at the level of glomeruli on the early stage of diabetes when proteinuria was not present and that C-peptide ameliorated this leakage. C-peptide, a byproduct of insulin secretion was once considered biologically inactive. Since as early as the 1980s, studies have provided direct evidence that C-peptide is a biologically active endogenous peptide hormone. It is now known that administration of physiologically relevant doses of C-peptide reduces diabetes-induced glomerular hyperfiltration, decreases albuminuria, and reduces renal hypertrophy. We hypothesised that C-peptide might work on the structure of glomerular filtration barrier to show its effects.We used streptozotocin-induced rats as diabetic animal models (50mg/kg). Part of both control and diabetic rats were given C-peptide continuously one hour prior to sacrifice (50pmol/kg/min). Extracted kidney samples were examined by fluorescence antibody technique and electron microscopy. Of glomerular slit membrane components, podocin, nephrin and CD2AP were stained and glomerular section images were binalised. The distribution of slit membrane proteins were analysed by area ratio (ratio for coexisting area of two component proteins). Inter-footprocess spaces were measured as podocytic structural change.There was a loose negative correlation between the diabetic duration and the area ratio of either two out of three protein components (r=-0.24 to -0.59). There was not a significant change in area ratio after C-peptide administration in both control and diabetic rats. The inter-footprocess spaces were significantly different (p<0.01), 8.17±0.44nm, 9.72±0.44nm for control and diabetic rats respectively. C-peptide administration widened the spaces to 10.39±0.65nm (p<0.01) and to 15.45±0.96nm (p<0.01) for control and diabetic rats respectively.C-peptide did not change the structure of glomerular slit membranes but widened the inter-footprocess spaces. C-peptide effects on ameliorating glomerular leakage of protein was considered to be due to other effects than causing structural changes to glomerular filtration barrier.