Proinsulin C-peptide constricts glomerular afferent arterioles in diabetic mice. A potential renoprotective mechanism

1 Department of Medical Cell Biology, Division of Physiology, University of Uppsala, Uppsala, Sweden; and 2 Johannes-Müller-Institute of Physiology, University Hospital Charité Humboldt-University of Berlin, Berlin, Germany Submitted 7 November 2007 ; accepted in final form 4 December 2007 Objective : an increased glomerular filtration rate (GFR) has been postulated as a potential mechanism involved in the progression of diabetic nephropathy. Studies suggest that C-peptide exerts a renoprotective effect on diabetes. The peptide decreases hyperfiltration in patients with type 1 diabetes, as well as in diabetic animal models. In this study, we investigated whether C-peptide causes a change in arteriolar diameter. Research Design and Methods : C57-Bl mice were made diabetic by means of a single intravenous injection of alloxan 2 wk prior to the experiment. Age-matched normoglycemic mice served as controls. Afferent arterioles, intact with the glomeruli, were dissected and microperfused. The effect of luminal application of C-peptide, compared with scrambled C-peptide or vehicle, was investigated. The effect of the Rho-kinase inhibitor Y-27632 was also investigated. Results : C-peptide constricted afferent arterioles in diabetic mice by –27% compared with the control value. Normoglycemic arterioles administered C-peptide displayed a delayed and minute response (–4%). Scrambled C-peptide or vehicle administration, whether administered to hyperglycemic or normoglycemic mice, did not induce any effect. Addition of Y-27632 abolished the effect of C-peptide. Conclusion : C-peptide induces constriction of afferent arterioles in diabetic mice. This can reduce enhanced GFR and may be one of the mechanisms in the renoprotective action of C-peptide in diabetes. diabetes; glomerular filtration rate; renal function Address for reprint requests and other correspondence: A. E. G. Persson, Uppsala Univ., Dept. of Medical Cell Biology, Biomedical Centre, Box 571, 751 23 Uppsala, Sweden (e-mail: Erik.Persson{at}mcb.uu.se )