Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Diabetes. 2009 Oct;58(10):2376-85. doi: 10.2337/db09-0047. Epub 2009 Jul 10.

Dyslipidemia-induced neuropathy in mice: the role of oxLDL/LOX-1.

Author information

  • 1Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA. andreav@umich.edu

Abstract

OBJECTIVE:

Neuropathy is a frequent and severe complication of diabetes. Multiple metabolic defects in type 2 diabetic patients result in oxidative injury of dorsal root ganglia (DRG) neurons. Our previous work focused on hyperglycemia clearly demonstrates induction of mitochondrial oxidative stress and acute injury in DRG neurons; however, this mechanism is not the only factor that produces neuropathy in vivo. Dyslipidemia also correlates with the development of neuropathy, even in pre-diabetic patients. This study was designed to explore the contribution of dyslipidemia in neuropathy.

RESEARCH DESIGN AND METHODS:

Mice (n = 10) were fed a control (10% kcal %fat) or high-fat (45% kcal %fat) diet to explore the impact of plasma lipids on the development of neuropathy. We also examined oxidized lipid-mediated injury in cultured DRG neurons from adult rat using oxidized LDLs (oxLDLs).

RESULTS:

Mice on a high-fat diet have increased oxLDLs and systemic and nerve oxidative stress. They develop nerve conduction velocity (NCV) and sensory deficits prior to impaired glucose tolerance. In vitro, oxLDLs lead to severe DRG neuron oxidative stress via interaction with the receptor lectin-like oxLDL receptor (LOX)-1 and subsequent NAD(P)H oxidase activity. Oxidative stress resulting from oxLDLs and high glucose is additive.

CONCLUSIONS:

Multiple metabolic defects in type 2 diabetes directly injure DRG neurons through different mechanisms that all result in oxidative stress. Dyslipidemia leads to high levels of oxLDLs that may injure DRG neurons via LOX-1 and contribute to the development of diabetic neuropathy.

PMID:
19592619
[PubMed - indexed for MEDLINE]
PMCID:
PMC2750230
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk