title: C-peptide preserves the renal microvascular architecture in the streptozotocin-induced diabetic rat.
abstract: OBJECTIVE
  C-peptide is renoprotective in type 1 diabetes, however, the mechanisms of its actions are not completely understood. We hypothesized that C-peptide attenuates diabetes-associated renal microvascular injury.
  
  
  METHODS
  After 4 or 8weeks of streptozotocin (STZ)-induced diabetes, rats received either vehicle or C-peptide in the presence of low or high doses of insulin. Urine albumin excretion (UAE) was measured prior to initiation of treatment (baseline) and 2 or 4weeks after treatment (sacrifice). Glomerular hypertrophy, glomerular filtration rate (GFR) and renal microvascular density, quantified ex vivo by 3D micro-CT reconstruction, were measured at sacrifice.
  
  
  RESULTS
  In rats receiving low doses of insulin, treatment with C-peptide reduced HbA1c levels by 24%. In these rats, the 107% increase in UAE rate from baseline to sacrifice in vehicle-treated rats was largely prevented with C-peptide. C-peptide also reduced diabetes-associated glomerular hyperfiltration by 30%, glomerular hypertrophy by 22% and increased the density of microvessels between 0 and 500μm in diameter by an average of 31% compared with vehicle-treated groups. Similar renoprotective effects of C-peptide were observed in rats treated with higher doses of daily insulin, despite no differences in HbA1c levels.
  
  
  CONCLUSIONS
  The study suggests that C-peptide is renoprotective by preserving the integrity of the renal microvasculature irrespective of glucose regulation.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Flynn
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lee
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Hutchens
authors.forename: Alejandro R
authors.initials: AR
authors.lastname: Chade
authors.forename: Christine
authors.initials: C
authors.lastname: Maric-Bilkan
mesh_terms: D000818:Animals; D002096:C-Peptide / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006984:Hypertrophy; D007328:Insulin / Q000008:administration & dosage; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D055806:Microvessels / Q000187:drug effects* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: D002096:C-Peptide; D007328:Insulin; D013311:Streptozocin
keywords: Blood vessels; Diabetes; Kidney; Rarefaction