Renoprotective effects of C-peptide in the Dahl salt-sensitive rat.
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.
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
R Taylor
RT
Sawyer
Elizabeth R
ER
Flynn
Zachary M
ZM
Hutchens
Jan M
JM
Williams
Michael R
MR
Garrett
Christine
C
Maric-Bilkan
D000419:Albuminuria / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D002096:C-Peptide / Q000008:administration & dosage*; D005355:Fibrosis; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D009395:Nephritis, Interstitial / Q000188:drug therapy / Q000473:pathology; D010539:Permeability / Q000187:drug effects; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D002096:C-Peptide; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D017673:Sodium Chloride, Dietary; D016212:Transforming Growth Factor beta