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C-Peptide Normalizes Glomerular Filtration Rate in Hyperfiltrating Conscious Diabetic Rats

  • Sara Stridh
  • Johan Sällström
  • Markus Fridén
  • Peter Hansell
  • Lina Nordquist
  • Fredrik Palm
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 645)

Abstract

Tubular electrolyte transport accounts for a major part of the oxygen consumed by the normal kidney. We have previously reported a close association between diabetes and increased oxygen usage, partly due to increased tubular electrolyte transport secondary to glomerular hyperfiltration during the early onset of diabetes. Several studies have shown that acute administration of C-peptide to diabetic rats with glomerular hyperfiltration results in normalized glomerular filtration rate (GFR). In this study, we validated a novel method for precise and repetitive GFR measurements in conscious rats and used C-peptide injection in diabetic rats for evaluation.

First, GFR was determined in normoglycemic control rats before and after C-peptide administration. Thereafter, all rats were made diabetic by an i.v. streptozotocin injection. Fourteen days later, GFR was again determined before and after C-peptide administration. GFR was estimated from plasma clearance curves using a single bolus injection of FITC-inulin, followed by serial blood sampling over 155 min. FITC-inulin clearance was calculated using non-compartmental pharmacokinetic data analysis. Baseline GFR in normoglycemic controls was 2.10±0.18 ml/min, and was unaffected by C-peptide (2.23±0.14 ml/min). Diabetic rats had elevated GFR (3.06±.034 ml/min), which was normalized by C-peptide (2.35±0.30 ml/min).

In conclusion, the used method for estimation of GFR in conscious animals result in values that are in good agreement with those obtained from traditional GFR measurements on anaesthetized rats. However, multiple measurements from the same conscious subject can be obtained using this method. Furthermore, as previously shown on anaesthetized rats, C-peptide also normalizes GFR in hyperfiltrating conscious diabetic rats.

Keywords

Glomerular Filtration Rate Diabetic Nephropathy Glomerular Hyperfiltration Glomerular Filtration Rate Measurement Single Bolus Injection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Sara Stridh
    • 1
  • Johan Sällström
    • 1
  • Markus Fridén
    • 2
  • Peter Hansell
    • 1
  • Lina Nordquist
    • 1
  • Fredrik Palm
    • 1
    • 3
  1. 1.Department of Medical Cell BiologyUppsala UniversitySweden
  2. 2.Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical BiosciencesUppsala UniversitySweden
  3. 3.Department of MedicineGeorgetown UniversityWashingtonUSA

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