Journal
DIABETES
Volume 57, Issue 6, Pages 1664-1673Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db07-1737
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- CIHR [72893] Funding Source: Medline
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OBJECTIVE-Peripheral neuropathy associated with type 2 diabetes (DPN) is not widely modeled. We describe unique features of DPN in type 2 diabetic Zucker diabetic fatty (ZDF) rats. RESEARCH DESIGN AND METHODS-We evaluated the structural, electrophysiological, behavioral, and molecular features of DPN in ZDF rats and littermates over 4 months of hyperglycemia. The status of insulin signaling transduction molecules that might be interrupted in type 2 diabetes and selected survival-, stress-, and pain-related molecules was emphasized in dorsal root ganglia (DRG) sensory neurons. RESULTS-ZDF rats developed slowing of motor sciatic-tibial and sensory sciatic digital conduction velocity and selective mechanical allodynia with preserved thermal algesia. Diabetic sural axons, preserved in number, developed atrophy, but there was loss of large-calibre dermal and small-calibre epidermal axons. In diabetic rats, insulin signal transduction pathways in lumbar DRGs were preserved or had trends toward upregulation: mRNA levels of insulin receptor beta-subunit (IR beta), insulin receptor substrate (IRS)-1, and IRS-2. The numbers of neurons expressing IRP protein were also preserved. There were trends toward early rises of mRNA levels of heat shock protein 27 (HSP27), the alpha 2 delta 1 calcium channel subunit, and phosphatidylinositol 3-kinase in diabetes. Others were unchanged, including nuclear factor-kappa B (NF-kappa B; p50/p105) and receptor for advanced glycosylation end-products (RAGE) as was the proportion of neurons expressing HSP27, NF-kappa B, and RAGE protein. CONCLUSIONS-ZDF type 2 diabetic rats develop a distal degenerative sensory neuropathy accompanied by a selective long-term pain syndrome. Neuronal insulin signal transduction molecules are preserved.
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