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)


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.


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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    N. A. Lassen, O. Munck, and J. H. Thaysen, Oxygen consumption and sodium reabsorption in the kidney, Acta Physiol Scand 51(371-84 (1961).PubMedCrossRefGoogle Scholar
  2. 2.
    M. Marre, M. Hallab, J. Roy, J. J. Lejeune, P. Jallet, and P. Fressinaud, Glomerular hyperfiltration in type I, type II, and secondary diabetes, J Diabetes Complications 6(1), 19-24 (1992).PubMedCrossRefGoogle Scholar
  3. 3.
    J. W. Yip, S. L. Jones, M. J. Wiseman, C. Hill, and G. Viberti, Glomerular hyperfiltration in the prediction of nephropathy in IDDM: a 10-year follow-up study, Diabetes 45(12), 1729-33 (1996).PubMedCrossRefGoogle Scholar
  4. 4.
    J. A. Staessen, J. Wang, G. Bianchi, and W. H. Birkenhager, Essential hypertension, Lancet 361(9369), 1629- 41 (2003).PubMedCrossRefGoogle Scholar
  5. 5.
    The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group, N Engl J Med 329(14), 977-86 (1993).CrossRefGoogle Scholar
  6. 6.
    K. A. Nath, S. M. Kren, and T. H. Hostetter, Dietary protein restriction in established renal injury in the rat. Selective role of glomerular capillary pressure in progressive glomerular dysfunction, J Clin Invest 78(5), 1199-205 (1986).PubMedCrossRefGoogle Scholar
  7. 7.
    C. Wojcikowski, V. Maier, K. Dominiak, R. Fussganger, and E. F. Pfeiffer, Effects of synthetic rat C-peptide in normal and diabetic rats, Diabetologia 25(3), 288-90 (1983).PubMedCrossRefGoogle Scholar
  8. 8.
    J. Wahren, K. Ekberg, B. Samnegard, and B. L. Johansson, C-peptide: a new potential in the treatment of diabetic nephropathy, Curr Diab Rep 1(3), 261-6 (2001).PubMedCrossRefGoogle Scholar
  9. 9.
    D. Y. Huang, K. Richter, A. Breidenbach, and V. Vallon, Human C-peptide acutely lowers glomerular hyperfiltration and proteinuria in diabetic rats: a dose-response study, Naunyn Schmiedebergs Arch Pharmacol 365(1), 67-73 (2002).PubMedCrossRefGoogle Scholar
  10. 10.
    L. Nordquist, E. Moe, and M. Sjoquist, The C-peptide fragment EVARQ reduces glomerular hyperfiltration in streptozotocin-induced diabetic rats, Diabetes Metab Res Rev, (2006).Google Scholar
  11. 11.
    B. Samnegard, S. H. Jacobson, B. L. Johansson, K. Ekberg, B. Isaksson, J. Wahren, and M. Sjoquist, Cpeptide and captopril are equally effective in lowering glomerular hyperfiltration in diabetic rats, Nephrol Dial Transplant 19(6), 1385-91 (2004).PubMedCrossRefGoogle Scholar
  12. 12.
    J. Wahren, K. Ekberg, and H. Jornvall, C-peptide is a bioactive peptide, Diabetologia 50(3), 503-9 (2007).PubMedCrossRefGoogle Scholar
  13. 13.
    L. Luzi, G. Zerbini, and A. Caumo, C-peptide: a redundant relative of insulin?, Diabetologia 50(3), 500-2 (2007).PubMedCrossRefGoogle Scholar
  14. 14.
    Z. Qi, I. Whitt, A. Mehta, J. Jin, M. Zhao, R. C. Harris, A. B. Fogo, and M. D. Breyer, Serial determination of glomerular filtration rate in conscious mice using FITC-inulin clearance, Am J Physiol Renal Physiol 286(3), F590-6 (2004).PubMedCrossRefGoogle Scholar
  15. 15.
    J. Gabrielsson, and D. Weiner, Non-compartmental Analysis, in: Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications, edited (Swedish Pharmaceutical Press, Stockholm, 2006), pp. 161-180.Google Scholar
  16. 16.
    F. Palm, J. Cederberg, P. Hansell, P. Liss, and P. O. Carlsson, Reactive oxygen species cause diabetesinduced decrease in renal oxygen tension, Diabetologia 46(8), 1153-60 (2003).PubMedCrossRefGoogle Scholar
  17. 17.
    C. Sturgeon, A. D. Sam, 2nd, and W. R. Law, Rapid determination of glomerular filtration rate by singlebolus inulin: a comparison of estimation analyses, J Appl Physiol 84(6), 2154-62 (1998).PubMedGoogle Scholar

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

Personalised recommendations