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Experimental Alcohol-Related Peripheral Neuropathy: Role of Insulin/IGF Resistance
Department of Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, 55 Claverick Street, Providence RI 02903, USA
Department of Neurology, Rhode Island Hospital, Alpert Medical School of Brown University, 593 Eddy Street, Providence RI 02903, USA
Departments of Neuropathology/Pathology, Neurology, Neurosurgery, and Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, 55 Claverick Street, Providence RI 02903, USA
* Author to whom correspondence should be addressed.
Received: 9 July 2012; in revised form: 30 July 2012 / Accepted: 2 August 2012 / Published: 17 August 2012
Abstract: 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.
Keywords: alcoholic peripheral neuropathy; insulin resistance; nerve conduction; experimental animal model; gene expression; demyelination; nutritional deficiency
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MDPI and ACS Style
Nguyen, V.A.; Le, T.; Tong, M.; Mellion, M.; Gilchrist, J.; de la Monte, S.M. Experimental Alcohol-Related Peripheral Neuropathy: Role of Insulin/IGF Resistance. Nutrients 2012, 4, 1042-1057.
Nguyen VA, Le T, Tong M, Mellion M, Gilchrist J, de la Monte SM. Experimental Alcohol-Related Peripheral Neuropathy: Role of Insulin/IGF Resistance. Nutrients. 2012; 4(8):1042-1057.
Nguyen, Van Anh; Le, Tran; Tong, Ming; Mellion, Michelle; Gilchrist, James; de la Monte, Suzanne M. 2012. "Experimental Alcohol-Related Peripheral Neuropathy: Role of Insulin/IGF Resistance." Nutrients 4, no. 8: 1042-1057.