title: Efficacy of a long-acting C-peptide analogue against peripheral neuropathy in streptozotocin-diabetic mice.
abstract: OBJECTIVE
  To investigate the efficacy of a pegylated C-peptide (Peg-C-peptide) against indices of peripheral neuropathy in a mouse model of type 1 diabetes and to compare efficacy of this C-peptide analogue against that of the native molecule.
  
  
  METHODS
  C57Bl/6 mice were injected with two consecutive doses of streptozotocin (STZ) to induce type 1 diabetes. Mice were treated twice daily with native C-peptide [0.4-1.3 mg/kg subcutaneously (s.c.)] or twice weekly with Peg-C-peptide (0.1-1.3 mg/kg s.c.) for 20 weeks. Motor and sensory nerve conduction velocities, thermal and tactile responses and rate dependent H-wave depression were assessed after 20 weeks of diabetes. Foot skin intraepidermal fibres and corneal nerves were counted, and sciatic nerve substance P and plasma C-peptide levels were also determined.
  
  
  RESULTS
  After 5 months of STZ-induced diabetes, mice exhibited significant motor and sensory nerve conduction slowing, thermal hypoalgesia, tactile allodynia and attenuation of rate-dependent depression of the H reflex. These functional disorders were accompanied by nerve substance P depletion but not loss of small sensory fibres in the hind paw epidermis or the cornea. The efficacy of twice-daily treatment with native C-peptide in preventing these disorders was matched or exceeded by twice-weekly treatment with Peg-C-peptide. Both native and Peg-C-peptide also increased corneal nerve occupancy in the sub-basal nerve plexus of control rats.
  
  
  CONCLUSIONS
  These data identify actions of C-peptide against novel and clinically pertinent aspects of diabetic neuropathy in mice and also establish Peg-C-peptide as a long-acting therapeutic method of potential clinical value.
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Jolivalt
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez
authors.affiliation: Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.|Cebix AB, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Wahren
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Calcutt
mesh_terms: D000818:Animals; D002096:C-Peptide / Q000032:analysis* / Q000097:blood / Q000494:pharmacology; D003315:Cornea / Q000294:innervation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D004334:Drug Administration Schedule; D004817:Epidermis / Q000294:innervation; D006614:Hindlimb / Q000294:innervation; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009431:Neural Conduction / Q000187:drug effects*; D051381:Rats; D012584:Sciatic Nerve / Q000378:metabolism
chemical_list: D002096:C-Peptide
keywords: C peptide; diabetic neuropathy; mouse model; type 1 diabetes