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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/R836    most recent 00811.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nordquist, L. Articles by Persson, A. E. G. Search for Related Content PubMed PubMed Citation Articles by Nordquist, L. Articles by Persson, A. E. G.

RENAL HEMODYNAMICS AND CARDIORENAL INTEGRATION

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

¹Department of Medical Cell Biology, Division of Physiology, University of Uppsala, Uppsala, Sweden; and ²Johannes-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