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

Abstract

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.