Nitrosamine Exposure Causes Insulin Resistance Diseases: Relevance to Type 2 Diabetes Mellitus, Non-Alcoholic Steatohepatitis, and Alzheimer's Disease
Year: 2009
Type: article
Abstract: The current epidemics of type 2 diabetes mellitus (T2DM), non-alcoholic steatohepatitis (NASH), and Alzheimer's disease (AD) all represent insulin-resistance diseases. Previous studies showed that streptozotocin, a nitrosamine-related com-pound, causes insulin resistance diseases including, T2DM, NASH, and AD-type neurodegeneration. We hypothesize that chronic human exposure to nitrosamine compounds, which are widely present in processed foods, contributes to the pathogenesis of T2DM, NASH, and AD. Long Evans rat pups were treated with N-nitrosodiethylamine (NDEA) by i.p. (x3) or i.c. (x1) injection, and 2-4 weeks later, they were evaluated for cognitive-motor dysfunction, insulin resistance, and neurodegeneration using behavioral, biochemical, and molecular approaches. NDEA treatment caused T2DM, NASH, deficits in motor function and spatial learning, and neurodegeneration characterized by insulin resistance and deficiency, lipid peroxidation, cell loss, increased levels of amyloid-beta protein precursor/amyloid-beta, phospho-tau, and ubiquitin immunoreactivities, and upregulated expression of pro-inflammatory cytokine and pro-ceramide genes, which together promote insulin resistance. In conclusion, environmental and food contaminant exposures to nitrosamines play critical roles in the pathogenesis of major insulin resistance diseases including T2DM, NASH, and AD. Improved detection and prevention of human exposures to nitrosamines will lead to earlier treatments and eventual quelling of these costly and devastating epidemics.
Source: Journal of Alzheimer s Disease
Institutions: Brown University, Rhode Island Hospital
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: G147029616, Midcareer Investigator Award in Alcohol-Related Human Disease Research, G3519709061, G4540679723, ETHANOL, INSULIN/IGF SIGNALING AND NEURONAL MIGRATION, EFFECTS OF ETHANOL ON INSULIN SIGNALING IN THE BRAIN, ALCOHOL EFFECTS ON THE LIVER, Ethanol, IRS-1 Signaling and Neuronal Migration, Alcohol Effects on the Liver, FASD Inhibition of ASPH-Notch Mediates Adolescent Cerebral White Matter Pathology-Potential Utility of Non-invasive Extracellular Vesicle Assays
OpenAlex ID: W4404638035