Review

Rev Diabet Stud, 2009, 6(3):203-210 DOI 10.1900/RDS.2009.6.203

C-Peptide: The Missing Link in Diabetic Nephropathy?

Lina Nordquist1, John Wahren2

1Department of Medical Cell Biology, Division of Integrative Physiology, Uppsala University, 75123 Uppsala, Sweden
2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Address correspondence to: lina.nordquist@mcb.uu.se

Manuscript submitted September 14, 2009; resubmitted October 2, 2009; accepted October 12, 2009.

Keywords: diabetes, C-peptide, nephropathy, microalbuminuria, glomerular hypertrophy, capillary pressure

Abstract

Proinsulin C-peptide has been found to exert beneficial effects in many tissues affected by diabetic microvascular complications, including the kidneys. Glomerular hyperfiltration and microalbuminuria are early markers of diabetic nephropathy. C-peptide at physiological concentrations effectively reduces diabetes-induced glomerular hyperfiltration via constriction of the afferent arteriole, dilation of the efferent arteriole, and inhibition of tubular reabsorption in experimental models of type 1 diabetes. The glomerular hypertrophy and mesangial matrix expansion seen in early diabetes can be reduced or prevented by C-peptide administration, possibly via interference with TGF-β1 and TNFα signaling. Several of C-peptide's reno-protective effects have been confirmed in human studies; reduced glomerular hyperfiltration and diminished urinary albumin excretion have been documented in type 1 diabetes patients receiving replacement doses of C-peptide for periods of up to 3 months. In this review, we critically summarize the current state of knowledge regarding C-peptide’s renal effects, and discuss possible mechanisms of its beneficial effects in diabetic nephropathy.

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