Distal Degenerative Sensory Neuropathy in a Long-Term Type 2 Diabetes Rat Model

• DOI: 10.2337/db07-1737
• Publication Date: 2008-03-11T00:49:46Z
• Authors: Valentine Brussee; GuiFang Guo; YingYing Dong; Chu Cheng; José A. Martinez; Darrell Smith; Gordon W. Glazner; Paul Fernyhough; Douglas W. Zochodne
• Keywords: Diabetic Neuropathy

OBJECTIVE—Peripheral neuropathy associated with type 2 diabetes (DPN) is not widely modeled. We describe unique features of DPN in diabetic Zucker fatty (ZDF) rats. RESEARCH DESIGN AND METHODS—We evaluated the structural, electrophysiological, behavioral, and molecular ZDF rats littermates over 4 months hyperglycemia. The status insulin signaling transduction molecules that might be interrupted selected survival-, stress-, pain-related was emphasized dorsal root ganglia (DRG) sensory neurons. RESULTS—ZDF developed slowing motor sciatic-tibial sciatic digital conduction velocity selective mechanical allodynia preserved thermal algesia. Diabetic sural axons, number, atrophy, but there loss large-calibre dermal small-calibre epidermal axons. In rats, signal pathways lumbar DRGs were or had trends toward upregulation: mRNA levels receptor β-subunit (IRβ), substrate (IRS)-1, IRS-2. numbers neurons expressing IRβ protein also preserved. There early rises heat shock 27 (HSP27), α2δ1 calcium channel subunit, phosphatidylinositol 3-kinase diabetes. Others unchanged, including nuclear factor-κB (NF-κB; p50/p105) for advanced glycosylation endproducts (RAGE) as proportion HSP27, NF-κB, RAGE protein. CONCLUSIONS—ZDF develop a distal degenerative accompanied by long-term pain syndrome. Neuronal are