[native-nutrition] carbs, insulin, and alzheimers
- Subject: carbs, insulin, and alzheimers
- From: Chris Masterjohn <chrismasterjohn@...>
- Date: Mon, 30 May 2005 17:32:36 -0400
- Yahoo! Message Number: 69107
- Onibasu Link: http://onibasu.com/archives/nn/69107.html
I was previously unaware of the link between high-carb diets, insulin
resistance, and alzheimers until I ran into these abstracts posted
below.
Chris
1: Med Hypotheses. 2004;62(5):689-700. Related Articles, Links
High carbohydrate diets and Alzheimer's disease.
Henderson ST.
Accera Inc. and Institute for Behavioral Genetics, University of
Colorado, 1480 30th Street, Boulder, CO 80303, USA.
samuel.henderson@...
Alzheimer's disease (AD) is a common, progressive, neurodegenerative
disease that primarily afflicts the elderly. A well-defined risk
factor for late onset AD is possession of one or more alleles of the
epsilon-4 variant (E4) of the apolipoprotein E gene. Meta-analysis of
allele frequencies has found that E4 is rare in populations with long
historical exposure to agriculture, suggesting that consumption of a
high carbohydrate (HC) diet may have selected against E4 carriers. The
apoE4 protein alters lipid metabolism in a manner similar to a HC
diet, suggesting a common mechanism for the etiology of AD.
Evolutionarily discordant HC diets are proposed to be the primary
cause of AD by two general mechanisms. (1) Disturbances in lipid
metabolism within the central nervous system inhibits the function of
membrane proteins such as glucose transporters and the amyloid
precursor protein. (2) Prolonged excessive insulin/IGF signaling
accelerates cellular damage in cerebral neurons. These two factors
ultimately lead to the clinical and pathological course of AD. This
hypothesis also suggests several preventative and treatment
strategies. A change in diet emphasizing decreasing dietary
carbohydrates and increasing essential fatty acids (EFA) may
effectively prevent AD. Interventions that restore lipid homeostasis
may treat the disease, including drugs that increase fatty acid
metabolism, EFA repletion therapy, and ketone body treatment.
1: FASEB J. 2004 May;18(7):902-4. Epub 2004 Mar 19. Related Articles, Links
Diet-induced insulin resistance promotes amyloidosis in a transgenic
mouse model of Alzheimer's disease.
Ho L, Qin W, Pompl PN, Xiang Z, Wang J, Zhao Z, Peng Y, Cambareri G,
Rocher A, Mobbs CV, Hof PR, Pasinetti GM.
Neuroinflammation Research Laboratories, Department of Psychiatry,
Mount Sinai School of Medicine, New York, New York, USA.
Recent epidemiological evidence indicates that insulin resistance, a
proximal cause of Type II diabetes [a non-insulin dependent form of
diabetes mellitus (NIDDM)], is associated with an increased relative
risk for Alzheimer's disease (AD). In this study we examined the role
of dietary conditions leading to NIDDM-like insulin resistance on
amyloidosis in Tg2576 mice, which model AD-like neuropathology. We
found that diet-induced insulin resistance promoted amyloidogenic
beta-amyloid (Abeta) Abeta1-40 and Abeta1-42 peptide generation in the
brain that corresponded with increased gamma-secretase activities and
decreased insulin degrading enzyme (IDE) activities. Moreover,
increased Abeta production also coincided with increased AD-type
amyloid plaque burden in the brain and impaired performance in a
spatial water maze task. Further exploration of the apparent
interrelationship of insulin resistance to brain amyloidosis revealed
a functional decrease in insulin receptor (IR)-mediated signal
transduction in the brain, as suggested by decreased IR beta-subunit
(IRbeta) Y1162/1163 autophosphorylation and reduced
phosphatidylinositol 3 (PI3)-kinase/pS473-AKT/Protein kinase (PK)-B in
these same brain regions. This latter finding is of particular
interest given the known inhibitory role of AKT/PKB on glycogen
synthase kinase (GSK)-3alpha activity, which has previously been shown
to promote Abeta peptide generation. Most interestingly, we found that
decreased pS21-GSK-3alpha and pS9-GSK-3beta phosphorylation, which is
an index of GSK activation, positively correlated with the generation
of brain C-terminal fragment (CTF)-gamma cleavage product of amyloid
precursor protein, an index of gamma-secretase activity, in the brain
of insulin-resistant relative to normoglycemic Tg2576 mice. Our study
is consistent with the hypothesis that insulin resistance may be an
underlying mechanism responsible for the observed increased relative
risk for AD neuropathology, and presents the first evidence to suggest
that IR signaling can influence Abeta production in the brain.
PMID: 15033922 [PubMed - indexed for MEDLINE]
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