C-peptide corrects endoneurial blood flow but not oxidative stress in type 1 BB/Wor rats.

  • Stevens M
  • Zhang W
  • Li F
 et al. 
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Oxidative stress and neurovascular dysfunction have emerged as contributing factors to the development of experimental diabetic neuropathy (EDN) in streptozotocin-diabetic rodents. Additionally, depletion of C-peptide has been implicated in the pathogenesis of EDN, but the mechanisms of these effects have not been fully characterized. The aims of this study were therefore to explore the effects of diabetes on neurovascular dysfunction and indexes of nerve oxidative stress in type 1 bio-breeding Worcester (BB/Wor) rats and type 2 BB Zucker-derived (ZDR)/Wor rats and to determine the effects of C-peptide replacement in the former. Motor and sensory nerve conduction velocities (NCVs), hindlimb thermal thresholds, endoneurial blood flow, and indicators of oxidative stress were evaluated in nondiabetic control rats, BB/Wor rats, BB/Wor rats with rat II C-peptide replacement (75 nmol C-peptide.kg body wt(-1).day(-1)) for 2 mo, and diabetes duration-matched BBZDR/Wor rats. Endoneurial perfusion was decreased and oxidative stress increased in type 1 BB/Wor rats. C-peptide prevented NCV and neurovascular deficits and attenuated thermal hyperalgesia. Inhibition of nitric oxide (NO) synthase, but not cyclooxygenase, reversed the C-peptide-mediated effects on NCV and nerve blood flow. Indexes of oxidative stress were unaffected by C-peptide. In type 2 BBZDR/Wor rats, neurovascular deficits and increased oxidative stress were unaccompanied by sensory NCV slowing or hyperalgesia. Therefore, nerve oxidative stress is increased and endoneurial perfusion decreased in type 1 BB/Wor and type 2 BBZDR/Wor rats. NO and neurovascular mechanisms, but not oxidative stress, appear to contribute to the effects of C-peptide in type 1 EDN. Sensory nerve deficits are not an inevitable consequence of increased oxidative stress and decreased nerve perfusion in a type 2 diabetic rodent model.

Author-supplied keywords

  • Animals
  • Body Weight
  • Body Weight: drug effects
  • C-Peptide
  • C-Peptide: pharmacology
  • Diabetic Nephropathies
  • Diabetic Nephropathies: pathology
  • Diabetic Nephropathies: physiopathology
  • Enzyme Inhibitors
  • Enzyme Inhibitors: pharmacology
  • Hindlimb
  • Hindlimb: blood supply
  • Hindlimb: innervation
  • Hot Temperature
  • Hyperalgesia
  • Hyperalgesia: physiopathology
  • Insulin
  • Insulin: deficiency
  • Lipid Peroxidation
  • Male
  • Motor Neurons
  • NG-Nitroarginine Methyl Ester
  • NG-Nitroarginine Methyl Ester: pharmacology
  • Nerve Tissue
  • Nerve Tissue: blood supply
  • Nerve Tissue: metabolism
  • Neural Conduction
  • Neural Conduction: drug effects
  • Neurons, Afferent
  • Oxidative Stress
  • Oxidative Stress: drug effects
  • Oxidoreductases
  • Oxidoreductases: metabolism
  • Rats
  • Rats, Inbred BB
  • Rats, Zucker
  • Reaction Time
  • Reaction Time: drug effects
  • Regional Blood Flow
  • Regional Blood Flow: drug effects

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  • Martin J Stevens

  • Weixian Zhang

  • Fei Li

  • Anders a F Sima

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