Proinsulin C-peptide constricts glomerular afferent arterioles in diabetic mice: A potential renoprotective mechanism
2008 (English)In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 294, no 3, R836-R841 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 294, no 3, R836-R841 p.
diabetes, glomerular filtration rate, renal function
IdentifiersURN: urn:nbn:se:uu:diva-104060DOI: 10.1152/ajpregu.00811.2007ISI: 000253778700019PubMedID: 18077505OAI: oai:DiVA.org:uu-104060DiVA: diva2:220131