Protective effect of C-peptide on experimentally induced diabetic nephropathy and the possible link between C-peptide and nitric oxide

Appl Physiol Nutr Metab. 2018 Jun;43(6):617-624. doi: 10.1139/apnm-2017-0617. Epub 2018 Jan 19.


Diabetic nephropathy one of the major microvascular diabetic complications. Besides hyperglycemia, other factors contribute to the development of diabetic complications as the proinsulin connecting peptide, C-peptide. We described the role of C-peptide replacement therapy on experimentally induced diabetic nephropathy, and its potential mechanisms of action by studying the role of nitric oxide (NO) as a mediator of C-peptide effects by in vivo modulating its production by NG-nitro-l-arginine methyl ester (L-NAME). Renal injury markers measured were serum urea, creatinine, tumor necrosis factor alpha, and angiotensin II, and malondialdehyde, total antioxidant, Bcl-2, and NO in renal tissue. In conclusion, diabetic induction resulted in islet degenerations and decreased insulin secretion with its metabolic consequences and subsequent renal complications. C-Peptide deficiencies in diabetes might have contributed to the metabolic and renal error, since C-peptide treatment to the diabetic rats completely corrected these errors. The beneficial effects of C-peptide are partially antagonized by L-NAME coadministration, indicating that NO partially mediates C-peptide effects.

Keywords: C-peptide; Nitric Oxide; diabetic nephropathy; néphropathie diabétique; oxyde nitrique; peptide C.

MeSH terms

  • Angiotensin II / blood
  • Animals
  • Biomarkers / blood
  • C-Peptide / pharmacology*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / pathology
  • Enzyme Inhibitors / pharmacology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / blood


  • Bcl2 protein, rat
  • Biomarkers
  • C-Peptide
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • Angiotensin II
  • Nitric Oxide
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester