Do đó, các rào cản kênh ion paranodal không phải là một cấu trúc cứng nhắc tĩnh nhưng chỉ đơn thuần là một phức tạp của protein-protein tương tác trao đổi chất theo quy định. Trong tiểu đường loại 1 BB / Wor-chuột biểu hiện của ankyrinG, contactin, RPTPβ, và β-Na + kênh tiểu đơn vị là không thay đổi gì sau 2 tháng của bệnh tiểu đường | 144 Sima et al. domains. p85 is the regulatory subunit of PI3-kinase and is probably mediated by insulin signaling Fig. 5 61 97 . Hence the paranodal ion-channel barrier is not a static rigid structure but merely a complex of metabolically regulated protein-protein interactions. In type 1 diabetic BB Wor-rat the expression of ankyrinG contactin RPTPp and P-Na -channel subunits are unaltered after 2 months of diabetes a time-point at which axoglial dysjunction is undetectable. However at 8 months of diabetes the expression of these molecules is significantly decreased. In addition the glycation of ankyrinG is increased coupled with decreased phosphorylation 61 the socalled yin-yang relationship hence compromising its protein-protein interaction. Interestingly the pore-forming a-Na channel expression is not altered. Of the paranodal constituents caspr is unaltered at 2 months but shows a 25 reduction in expression at 8 months at which time there is also marked suppression of contactin and RPTPP 61 . Similar changes are not detectable in 8-month BBZDR Wor-rats 61 suggesting that these aberrations in type 1 diabetes are associated with impaired insulin signaling. Indirect evidence for this construct is provided by the beneficial effects of insulinomimetic C-peptide 48 61 which prevents both the impaired expression of these molecular elements and maximizes their perturbed post-translational modifications necessary for protein-protein interaction. However more chronic 14-month diabetic BBZDR Wor-rats do show evidence of nodal and paranodal degenerative changes such as significant paranodal demyelination and increased frequencies of intercalated internodes 31 . Therefore the progressive axoglial dysjunction first evident after 4 months of diabetes in the BB Wor-rats has a molecular underpinning that appears to be caused by impaired insulin signaling thereby explaining the differences between DPN in type 1 and type 2 diabetes with respect to nodal and paranodal pathology.
