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Metabolic-Functional-Structural Correlations in Somatic Neuropathies in the Spontaneously Type 1 and Type 2 Diabetic BB-Rats

  • Chapter
Diabetic Neuropathy

Part of the book series: Clinical Diabetes ((CLD))

Abstract

Diabetic neuropathy (DPN) is a dynamic condition affecting both type 1 and type 2 diabetic subjects. It can be divided into an early and reversible metabolic phase of nerve dysfunction. This is caused by hyperglycemia-induced activation of the polyol-pathway, redox imbalances as well as by insulin/C-peptide deficiencies resulting in impaired neural Na+/K+-ATPase activity and impairment of endoneurial blood flow. Superimposed on these metabolic abnormalities, progressive structural changes evolve which become increasingly resistant to therapeutic interventions. These affect both unmyelinated and myelinated fiber populations and consist of axonal atrophy, degeneration, and loss occurring in a dying-back fashion. The underlying mechanisms include impaired neurotrophic support including perturbed insulin/C-peptide signaling, resulting in suppressed expression of neuroskeletal protein genes, and aberrant phosphorylation of these axonal building blocks. Both the early metabolic and later occurring molecular abnormalities underlying the structural abnormalities are more severely affected in type 1 DPN relating to insulin and C-peptide deficiencies, which are not present in type 2 diabetes. This distinction between the two forms of DPN also underlies nodal and paranodal degeneration unique to both human and experimental type 1 DPN. Impaired insulin action affects the expression of nodal and paranodal adhesive molecules and their post-translational modifications. Such aberrations result in disruption of the paranodal barrier function with decreased nodal Na+-channels densities and worsening of the nerve conduction defect in type 1 DPN. In conclusion, major differences exist between type 1 and type 2 DPN, which can be directly related to the absence and presence of insulin action.

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Authors and Affiliations

  1. Department of Pathology, Wayne State University, Detroit, MI

    Anders A. F. Sima, Weixian Zhang & Hideki Kamiya

  2. Department of Neurology, Wayne State University, Detroit, MI

    Anders A. F. Sima

  3. The Morris Hood Comprehensive Diabetes Centre, Wayne State University, Detroit, MI

    Anders A. F. Sima

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  1. Anders A. F. Sima
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  2. Weixian Zhang
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  3. Hideki Kamiya
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Editors and Affiliations

  1. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

    Aristidis Veves MD, DSc

  2. Manchester Royal Infirmary and University of Manchester, Manchester, UK

    Rayaz A. Malik MBChB, PhD

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Sima, A.A.F., Zhang, W., Kamiya, H. (2007). Metabolic-Functional-Structural Correlations in Somatic Neuropathies in the Spontaneously Type 1 and Type 2 Diabetic BB-Rats. In: Veves, A., Malik, R.A. (eds) Diabetic Neuropathy. Clinical Diabetes. Humana Press. https://doi.org/10.1007/978-1-59745-311-0_8

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  • DOI: https://doi.org/10.1007/978-1-59745-311-0_8

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