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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/F1265    most recent 00228.2009v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Nordquist, L. Articles by Palm, F. PubMed PubMed Citation Articles by Nordquist, L. Articles by Palm, F.

Proinsulin C-peptide reduces diabetes-induced glomerular hyperfiltration via efferent arteriole dilation and inhibition of tubular sodium reabsorption

¹Division of Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden; ; ²Department of Physiology, Monash University, Melbourne, Australia; and ; ³Division of Nephrology and Hypertension, Department of Medicine, Georgetown University, Washington, District of Columbia

Submitted April 27, 2009 ; accepted in final form September 8, 2009

C-peptide reduces diabetes-induced glomerular hyperfiltration in diabetic patients and experimental animal models. However, the mechanisms mediating the beneficial effect of C-peptide remain unclear. We investigated whether altered renal afferent-efferent arteriole tonus or alterations in tubular Na⁺ transport (T_Na) in response to C-peptide administration mediate the reduction of diabetes-induced glomerular hyperfiltration. Glomerular filtration rate, filtration fraction, total and cortical renal blood flow, total kidney O₂ consumption (QO₂), T_Na, fractional Na⁺ and Li⁺ excretions, and tubular free-flow and stop-flow pressures were measured in anesthetized adult male normoglycemic and streptozotocin-diabetic Sprague-Dawley rats. The specific effect of C-peptide on transport-dependent QO₂ was investigated in vitro in freshly isolated proximal tubular cells. C-peptide reduced glomerular filtration rate (–24%), stop-flow pressure (–8%), and filtration fraction (–17%) exclusively in diabetic rats without altering renal blood flow. Diabetic rats had higher baseline T_Na (+40%), which was reduced by C-peptide. Similarly, C-peptide increased fractional Na⁺ (+80%) and Li⁺ (+47%) excretions only in the diabetic rats. None of these parameters was affected by vehicle treatments in either group. Baseline QO₂ was 37% higher in proximal tubular cells from diabetic rats than controls and was normalized by C-peptide. C-peptide had no effect on ouabain-pretreated diabetic cells from diabetic rats. C-peptide reduced diabetes-induced hyperfiltration via a net dilation of the efferent arteriole and inhibition of tubular Na⁺ reabsorption, both potent regulators of the glomerular net filtration pressure. These findings provide new mechanistic insight into the beneficial effects of C-peptide on diabetic kidney function.

diabetes mellitus; oxygen consumption; sodium excretion