title: C-peptide prevents and improves chronic Type I diabetic polyneuropathy in the BB/Wor rat.
abstract: OBJECTIVE
  Insulin and C-peptide exert neuroprotective effects and are deficient in Type I (insulin-dependent) diabetes mellitus but not in Type II (non-insulin-dependent) diabetes mellitus. These studies were designed to test the preventive and interventional effects of C-peptide replacement on diabetic polyneuropathy in the Type I diabetic BB/Wor rat.
  
  
  METHODS
  Diabetic BB/Wor rats were replaced with rat C-peptide from onset of diabetes and between 5 and 8 months of diabetes. They were examined at 2 and 8 months and compared to non-C-peptide replaced BB/Wor rats, Type II diabetic (non-C-peptide deficient) BB/Z rats and non-diabetic control rats. Animals were monitored as to hyperglycaemia and nerve conduction velocity (NCV). Acute changes such as neural Na+/K+-ATPase and paranodal swelling were examined at 2 months, morphometric and teased fiber analyses were done at 8 months.
  
  
  RESULTS
  C-peptide replacement for 2 months in Type I diabetic rats prevented the acute NCV defect by 59% (p < 0.005), the neural Na+/K+-ATPase defect by 55% (p < 0.001) and acute paranodal swelling by 61% (p < 0.001). Eight months of C-peptide replacement prevented the chronic nerve conduction defect by 71% (p < 0.001) and totally prevented axoglial dysjunction (p < 0.001) and paranodal demyelination (p < 0.001). C-peptide treatment from 5 to 8 months showed a 13% (p < 0.05) improvement in NCV, a 33% (p < 0.05) improvement in axoglial dysjunction, normalization (p < 0.001) of paranodal demyelination, repair of axonal degeneration (p < 0.01), and a fourfold (p < 0.001) increase in nerve fibre regeneration.
  
  
  CONCLUSIONS
  C-peptide replacement of Type I BB/Wor-rats partially prevents acute and chronic metabolic, functional and structural changes that separate Type I diabetic polyneuropathy from its Type II counterpart suggesting that C-peptide deficiency plays a pathogenetic role in Type I diabetic polyneuropathy.
authors.affiliation: Department of Pathology, Wayne State University, Detroit, Michigan 48201, USA. asima@med.wayne.edu
authors.forename: A A
authors.initials: AA
authors.lastname: Sima
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Sugimoto
authors.forename: D
authors.initials: D
authors.lastname: Henry
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Wahren
authors.forename: G
authors.initials: G
authors.lastname: Grunberger
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D002096:C-Peptide / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D009186:Myelin Sheath / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011913:Rats, Inbred BB; D013997:Time Factors
chemical_list: D002096:C-Peptide