Physiological doses of homologous C-peptide prevent the development of glomerular hypertrophy, albuminuria, and glomerular hyperfiltration in rats with experimentally induced diabetes.

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 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.

C-peptide is formed in the biosynthesis of insulin and the two peptides are subsequently released in equimolar amounts to the circulation. C-peptide has long been considered to be without physiologic effects. Recent data now demonstrate that C-peptide in the nanomolar concentration range binds specifically to cell surfaces, probably to G protein-coupled receptors, with subsequent activation of Ca(2+)-dependent intracellular signaling pathways and stimulation of Na+, K(+)-ATPase activities. C-peptide replacement in animal models of type 1 diabetes results in diminished hyperfiltration, improved functional reserve, reduction of urinary albumin excretion, and prevention of glomerular and renal hypertrophy. Administration of C-peptide to physiologic concentrations in patients with type 1 diabetes and incipient nephropathy for periods of 3 hours to 3 months is accompanied by reduced glomerular hyperfiltration and filtration fraction, and diminished urinary albumin excretion. C-peptide replacement together with insulin therapy may be beneficial in type 1 diabetes patients with nephropathy.

It was recently shown that the early rise in arterial insulin concentration after an oral glucose meal is largely because of a decreased extraction of the hormone. The kidney is a major site for extraction of insulin and C-peptide. We therefore measured the renal extraction of insulin and C-peptide in eight healthy individuals before and after ingestion of 75 g of glucose. Arterial, renal venous and hepatic venous catheters were inserted. Splanchnic and renal plasma flow were measured, as well as arterial, hepatic venous and renal venous concentrations of insulin and C-peptide. Renal fractional extraction of insulin increased significantly, from 21% to a maximum of 48% after the meal while the renal fractional extraction of C-peptide did not change significantly. Renal blood flow decreased slightly but significantly after the meal. It is concluded that renal fractional extraction of insulin increases and that renal blood flow decreases after a glucose meal.