Renoprotective effects of C-peptide in the Dahl salt-sensitive rat.

Abstract

Previous studies have demonstrated that renoprotective effects of C-peptide in experimental models of diabetes-induced renal disease may be mediated via lowering blood glucose. The present study examined the renoprotective effects of C-peptide in a model of nondiabetic renal disease, the Dahl salt-sensitive (SS/jr) rat. SS/jr rats were placed on a 2% NaCl diet for 2 wk (HS2, resulting in mild to moderate renal injury) or 4 wk (HS4, resulting in advanced renal injury) and then received either vehicle (veh) or C-peptide (Cpep) for additional 4 wk. Urine albumin (UAE) and protein (UPE) excretion rates were measured at baseline (i.e., before initiation of veh or Cpep treatment) and 4 wk later (i.e., at the time of death). Glomerular permeability, indexes of glomerulosclerosis and tubulointerstitial fibrosis, the presence of inflammatory cells, and protein expression of transforming growth factor-β (TGF-β) and podocin were measured at the time of death. In HS2 + veh rats, UAE and UPE increased by 74 and 92%, respectively, from baseline and the time of death. While HS2 + Cpep attenuated this increase in UAE and UPE, HS4 + Cpep had no effect on these parameters. Similarly, HS2 + Cpep reduced glomerular permeability, tubulointerstitial fibrosis, renal inflammation, TGF-β, and podocin protein expression, while HS4 + Cpep had no effect. These studies indicate that C-peptide is renoprotective in nondiabetic experimental models with mild to moderate renal injury.

• Authors: R Taylor Sawyer, Elizabeth R Flynn, Zachary M Hutchens Jr, Jan M Williams, Michael R Garrett, Christine Maric-Bilkan
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 303 Issue 6 Pg. F893-9 (Sep 15 2012) ISSN: 1522-1466 [Electronic] United States
• PMID: 22811482 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• C-Peptide
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• NPHS2 protein
• Sodium Chloride, Dietary
• Transforming Growth Factor beta

Topics

• Albuminuria (drug therapy, pathology)
• Animals
• C-Peptide (administration & dosage)
• Fibrosis
• Glomerulosclerosis, Focal Segmental (drug therapy, pathology)
• Intracellular Signaling Peptides and Proteins (biosynthesis)
• Kidney Glomerulus (drug effects, pathology)
• Male
• Membrane Proteins (biosynthesis)
• Nephritis, Interstitial (drug therapy, pathology)
• Permeability (drug effects)
• Rats
• Rats, Inbred Dahl
• Sodium Chloride, Dietary (adverse effects)
• Transforming Growth Factor beta (biosynthesis)