Diabetes & C-Peptide by Anders A.F. Sima

Author:Anders A.F. Sima
Language: eng
Format: epub
Publisher: Humana Press, Totowa, NJ

Nodal and Paranodal Degeneration and C-Peptide

A characteristic abnormality occurring in type 1 DPN in humans and animal models is progressive degeneration of the nodal and paranodal apparati [10, 79–81]. The paranodal tight junctions adhering the terminal myelin loops to the paranodal axolemma, and comprise the paranodal ion-channel barrier, important for the normal placement and confinement of α-Na+-channels to the nodal axolemma. The progressive degeneration and breakdown of this barrier in type 1 DPN allows for lateralization of the α-Na-channels away from the node and correlates with the chronic less reversible nerve conduction defect [75, 81–83].

As mentioned above, this barrier system is made up of a series of interacting adhesive proteins. Not only are these structural proteins, like caspr, contactin, and RPTB-β downregulated in type 1 DPN, but their binding to each other and activation are perturbed. So, for instance, the phosphorylation of RPTB-β and the binding of p85 to the SH3 domains of caspr are compromised, abnormalities which are caused by impaired insulin signaling [84–87]. Full C-peptide replacement in the BB/Wor-rat prevents and corrects the underlying molecular defects and restores the structural integrity of the ion-channel barrier (Fig. 8.3) [45].

Fig. 8.3Morphometric assessment of axoglial junction loss. Note in control rats about 10% of axoglial junctions are not closed (C5 and C8). In nontreated diabetic rats there was a progressive loss of paranodal junctions from 5 to 8 months duration of diabetes (D1-5 and D1-8). Rats treated with full C-peptide replacement from onset of diabetes (DICP) showed a significant prevention of axoglial dysjunction. Animals treated with full C-peptide replacement from 5 to 8 months of diabetes (DICP 5/8) showed significant repair of paranodal junctions (adapted from ref. [91])

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