Abstract:
:Diabetic polyneuropathy (DPN) shows more severe functional and structural changes in type 1 than in type 2 human and experimental diabetes. We have previously suggested that these differences may be due to insulin and/or C-peptide deficiencies in type 1 diabetes. To further explore these differences between type I and type 2 DPN, we examined factors underlying nerve fiber regeneration in the hyperinsulinemic type 2 BB/Z-rat and compared these with previous data obtained from the iso-hyperglycemic, insulin and C-peptide-deficient type 1 diabetic BB/Wor-rat. The expression of neurotrophic factors and cytoskeletal proteins were studied in L4 and L5 dorsal root ganglia (DRG) at various time points after sciatic nerve crush. The data were compared to those of nondiabetes-prone BB-rats. Insulin-like growth factor 1 (IGF-1) and TrkA levels were lower in DRG from type 1 than from those of type 2 and control BB-rats. On the other hand, IGF-1 receptor expression was increased at baseline in type 1 BB/Wor-rats and decreased after crush injury, whereas its expression increased after crush injury in both control and type 2 BB/Z-rats. Following crush injury, betaII- and betaIII-tubulins were upregulated in type 2 BB/Z and control rats, which did not occur in type 1 BB/Wor-rats. Furthermore, type 2 BB/Z-rats showed the normal downregulation of low and medium molecular neurofilament (NF-L and NF-M, respectively), which did not occur in type 1 BB/Wor-rats. These findings were associated with significantly milder abnormalities in axonal elongation and caliber growth of regenerating fibers in type 2 compared to type 1 diabetic rats. These data suggest that impaired insulin signaling in type 1 diabetic nerve may be of greater significance in the regulation of neurotrophic and neurocytoskeletal protein synthesis than hyperglycemia in explaining the differences in nerve fiber regeneration between type 2 and type 1 diabetes.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Pierson CR,Zhang W,Murakawa Y,Sima AAdoi
10.1093/jnen/62.3.260subject
Has Abstractpub_date
2003-03-01 00:00:00pages
260-71issue
3eissn
0022-3069issn
1554-6578journal_volume
62pub_type
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