RGD Reference Report - Experimental alcohol-related peripheral neuropathy: role of insulin/IGF resistance. - Rat Genome Database

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Experimental alcohol-related peripheral neuropathy: role of insulin/IGF resistance.

Authors: Nguyen, VA  Le, T  Tong, M  Mellion, M  Gilchrist, J  De la Monte, SM 
Citation: Nguyen VA, etal., Nutrients. 2012 Aug;4(8):1042-57. Epub 2012 Aug 17.
RGD ID: 10402569
Pubmed: (View Article at PubMed) PMID:23016131
DOI: Full-text: DOI:10.3390/nu4081042

The mechanisms of alcohol-related peripheral neuropathy (ALPN) are poorly understood. We hypothesize that, like alcohol-related liver and brain degeneration, ALPN may be mediated by combined effects of insulin/IGF resistance and oxidative stress. Adult male Long Evans rats were chronically pair-fed with diets containing 0% or 37% ethanol (caloric), and subjected to nerve conduction studies. Chronic ethanol feeding slowed nerve conduction in the tibial (p = 0.0021) motor nerve, and not plantar sensory nerve, but it did not affect amplitude. Histological studies of the sciatic nerve revealed reduced nerve fiber diameters with increased regenerative sprouts, and denervation myopathy in ethanol-fed rats. qRT-PCR analysis demonstrated reduced mRNA levels of insulin, IGF-1, and IGF-2 polypeptides, IGF-1 receptor, and IRS2, and ELISAs revealed reduced immunoreactivity for insulin and IGF-1 receptors, IRS-1, IRS-4, myelin-associated glycoprotein, and tau in sciatic nerves of ethanol-fed rats (all p < 0.05 or better). The findings suggest that ALPN is characterized by (1) slowed conduction velocity with demyelination, and a small component of axonal degeneration; (2) impaired trophic factor signaling due to insulin and IGF resistance; and (3) degeneration of myelin and axonal cytoskeletal proteins. Therefore, ALPN is likely mediated by molecular and signal transduction abnormalities similar to those identified in alcoholic liver and brain degeneration.

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Igf1  (insulin-like growth factor 1)
Igf1r  (insulin-like growth factor 1 receptor)
Igf2  (insulin-like growth factor 2)

Genes (Mus musculus)
Igf1  (insulin-like growth factor 1)
Igf1r  (insulin-like growth factor I receptor)
Igf2  (insulin-like growth factor 2)

Genes (Homo sapiens)
IGF1  (insulin like growth factor 1)
IGF1R  (insulin like growth factor 1 receptor)
IGF2  (insulin like growth factor 2)

Additional Information