PMID- 20387270
OWN - NLM
STAT- MEDLINE
DCOM- 20100922
LR  - 20220408
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Print)
IS  - 1387-2877 (Linking)
VI  - 17
IP  - 4
DP  - 2009
TI  - Nitrosamine exposure causes insulin resistance diseases: relevance to type 2 
      diabetes mellitus, non-alcoholic steatohepatitis, and Alzheimer's disease.
PG  - 827-44
AB  - 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.
FAU - Tong, Ming
AU  - Tong M
AD  - Department of Pathology, Rhode Island Hospital, Warren Alpert Medical School of 
      Brown University, Providence, RI 02903, USA.
FAU - Neusner, Alexander
AU  - Neusner A
FAU - Longato, Lisa
AU  - Longato L
FAU - Lawton, Margot
AU  - Lawton M
FAU - Wands, Jack R
AU  - Wands JR
FAU - de la Monte, Suzanne M
AU  - de la Monte SM
LA  - eng
GR  - AA-12908/AA/NIAAA NIH HHS/United States
GR  - AA-11431/AA/NIAAA NIH HHS/United States
GR  - R56 AA011431/AA/NIAAA NIH HHS/United States
GR  - K24 AA016126-05/AA/NIAAA NIH HHS/United States
GR  - R37 AA011431-13/AA/NIAAA NIH HHS/United States
GR  - R37 AA002666/AA/NIAAA NIH HHS/United States
GR  - K24 AA016126-04/AA/NIAAA NIH HHS/United States
GR  - R37 AA011431/AA/NIAAA NIH HHS/United States
GR  - R01 AA012908/AA/NIAAA NIH HHS/United States
GR  - K24 AA016126-03/AA/NIAAA NIH HHS/United States
GR  - R01 AA012908-06A1S1/AA/NIAAA NIH HHS/United States
GR  - AA-02666/AA/NIAAA NIH HHS/United States
GR  - R01 AA011431/AA/NIAAA NIH HHS/United States
GR  - R01 AA012908-08/AA/NIAAA NIH HHS/United States
GR  - R37 AA011431-12A1/AA/NIAAA NIH HHS/United States
GR  - K24 AA016126/AA/NIAAA NIH HHS/United States
GR  - R01 AA012908-07/AA/NIAAA NIH HHS/United States
GR  - R01 AA002666/AA/NIAAA NIH HHS/United States
GR  - R56 AA011431-12/AA/NIAAA NIH HHS/United States
GR  - K24-AA-16126/AA/NIAAA NIH HHS/United States
GR  - AA-02169/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Ceramides)
RN  - 0 (Cytokines)
RN  - 0 (Ubiquitin)
RN  - 0 (tau Proteins)
RN  - 3IQ78TTX1A (Diethylnitrosamine)
SB  - IM
MH  - Alzheimer Disease/chemically induced/*metabolism
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Animals, Newborn
MH  - Ceramides/genetics/metabolism
MH  - Cognition/*drug effects
MH  - Cytokines/genetics/metabolism
MH  - Diabetes Mellitus, Type 2/chemically induced/*metabolism
MH  - Diethylnitrosamine/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Fatty Liver/chemically induced/*metabolism
MH  - Injections, Intraperitoneal
MH  - *Insulin Resistance
MH  - Lipid Peroxidation
MH  - Microinjections
MH  - Motor Activity/drug effects
MH  - Nerve Degeneration/*chemically induced/metabolism
MH  - Psychomotor Performance/*drug effects
MH  - Rats
MH  - Rats, Long-Evans
MH  - Space Perception/drug effects
MH  - Time Factors
MH  - Ubiquitin/metabolism
MH  - tau Proteins/metabolism
PMC - PMC2952429
MID - NIHMS230386
EDAT- 2009/01/01 00:00
MHDA- 2010/09/24 06:00
PMCR- 2010/10/11
CRDT- 2010/04/14 06:00
PHST- 2010/04/14 06:00 [entrez]
PHST- 2009/01/01 00:00 [pubmed]
PHST- 2010/09/24 06:00 [medline]
PHST- 2010/10/11 00:00 [pmc-release]
PST - ppublish
SO  - J Alzheimers Dis. 2009;17(4):827-44.