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 -- J.R.R. Tolkien The Children of Hurin
- Glucose Metabolism -


General Information:

Names:
Wikipedia entry:
Dr. Ray Shahelien entry: 

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Observations:

Type III Diabetes

See also Coconut Oil, Cinnamon, Methylene Blue

[Need more info-- research in Canada-- Certain diabetes drugs help? -- Basic idea is that brain cells don't metabolize sugar well, leading to build-up of AB plaques.  Also find info on recent research indicating that pancreatic diabetes (types I & II) can be caused by malfunctioning nerve cells in the pancrease.  I wonder if these two are related?]

Getting Diabetes Before 65 More Than Doubles Risk For Alzheimer's Disease
ScienceDaily (Jan. 28, 2009)
"Diabetics have a significantly greater risk of dementia, both Alzheimer's disease — the most common form of dementia — and other dementia, reveals important new data from an ongoing study of twins. The risk of dementia is especially strong if the onset of diabetes occurs in middle age, according to the study..."
http://www.sciencedaily.com/releases/2009/01/090127152835.htm

Related article appearing February 3, 2009 on ScienceDaily.com about AD as a "type 3 diabetes".

So, the question is, does cinnamon help with sugar metabolism, or with preventing and reversing tau protein corruption? Or both? Is there enough of the tau-buster chemical in the typical quantity of cinnamon people have been taking (about 1/2 tsp) to be effective?

When the news about this "water-soluble component of common cinnamon" first appeared last year, this was pretty much our only option to fight tau corruption. Since then, we've learned about methylene blue and niacinamide. For improving sugar metabolism, we now know about MCT oil and coconut oil.  See also Tau Busters.

Here's the article:

Insulin Is A Possible New Treatment For Alzheimer's
ScienceDaily (Feb. 3, 2009)
"A Northwestern University-led research team reports that insulin, by shielding memory-forming synapses from harm, may slow or prevent the damage and memory loss caused by toxic proteins in Alzheimer's disease. The findings, which provide additional new evidence that Alzheimer's could be due to a novel third form of diabetes, will be published online the week of Feb. 2 by the Proceedings of the National Academy of Sciences (PNAS)..."
http://www.sciencedaily.com/releases/2009/02/090202174818.htm

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Diabetes and Dementia

See also Metformin, Cinnamon,

Substance in Tangerines Fights Obesity and Protects Against Heart Disease, Research Suggests

ScienceDaily (Apr. 6, 2011) — New research from The University of Western Ontario has discovered a substance in tangerines not only helps to prevent obesity, but also offers protection against type 2 diabetes, and even atherosclerosis, the underlying disease responsible for most heart attacks and strokes... "The Nobiletin-treated mice were basically protected from obesity. And in longer-term studies, Nobiletin also protected these animals from atherosclerosis, the buildup of plaque in arteries, which can lead to a heart attack or stroke. This study really paves the way for future studies to see if this is a suitable treatment for metabolic syndrome and related conditions in people."
http://www.sciencedaily.com/releases/2011/04/110406161030.htm


Nobiletin Attenuates VLDL Overproduction, Dyslipidemia, and Atherosclerosis in Mice With Diet-Induced Insulin Resistance.
Diabetes. 2011 Apr 6.
Mulvihill EE, Assini JM, Lee JK, Allister EM, Sutherland BG, Koppes JB, Sawyez CG, Edwards JY, Telford DE, Charbonneau A, St-Pierre P, Marette A, Huff MW.

Vascular Biology, Robarts Research Institute, London, Ontario, Canada.
Abstract

OBJECTIVE Increased plasma concentrations of apolipoprotein B100 often present in patients with insulin resistance and confer increased risk for the development of atherosclerosis. Naturally occurring polyphenolic compounds including flavonoids have antiatherogenic properties. The aim of the current study was to evaluate the effect of the polymethoxylated flavonoid nobiletin on lipoprotein secretion in cultured human hepatoma cells (HepG2) and in a mouse model of insulin resistance and atherosclerosis. RESEARCH DESIGN AND METHODS Lipoprotein secretion was determined in HepG2 cells incubated with nobiletin or insulin. mRNA abundance was evaluated by quantitative RT-PCR, and Western blotting was used to demonstrate activation of cell signaling pathways. In LDL receptor-deficient mice (Ldlr(-/-)) fed a Western diet supplemented with nobiletin, metabolic parameters, gene expression, fatty acid oxidation, glucose homeostasis, and energy expenditure were documented. Atherosclerosis was quantitated by histological analysis. RESULTS In HepG2 cells, activation of mitogen-activated protein kinase-extracellular signal-related kinase signaling by nobiletin or insulin increased LDLR and decreased MTP and DGAT1/2 mRNA, resulting in marked inhibition of apoB100 secretion. Nobiletin, unlike insulin, did not induce phosphorylation of the insulin receptor or insulin receptor substrate-1 and did not stimulate lipogenesis. In fat-fed Ldlr(-/-) mice, nobiletin attenuated dyslipidemia through a reduction in VLDL-triglyceride (TG) secretion. Nobiletin prevented hepatic TG accumulation, increased expression of Pgc1α and Cpt1α, and enhanced fatty acid β-oxidation. Nobiletin did not activate any peroxisome proliferator-activated receptor (PPAR), indicating that the metabolic effects were PPAR independent. Nobiletin increased hepatic and peripheral insulin sensitivity and glucose tolerance and dramatically attenuated atherosclerosis in the aortic sinus. CONCLUSIONS Nobiletin provides insight into treatments for dyslipidemia and atherosclerosis associated with insulin-resistant states.

PMID: 21471511 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21471511

Type-2 diabetes linked to autoimmune reaction in study
APRIL 17, 2011
Stanford School of Medicine
...Nearly all type-2 diabetes drugs marketed today are designed to control a patient’s high blood sugar levels — a symptom of the body’s inability to respond properly to insulin. However, the researchers found that anti-CD20, which targets and eliminates mature B cells, could completely head off the development of type-2 diabetes in laboratory mice prone to the disorder and restore their blood sugar levels to normal. The researchers believe that insulin resistance arises when the B cells and other immune cells react against the body’s own tissues... Several years ago, Daniel and Shawn Winer began to speculate that different types of immune cells, including T cells and B cells, can cause inflammation in the fatty tissue that surrounds and cushions organs in the body. This inflammation occurs in mice fed a high-fat, high-calorie diet when the rapidly growing fat cells outstrip their blood supply and begin to die. (It’s also seen in humans with type-2 diabetes.) The dying cells spew their contents, and immune system cells called macrophages are summoned to clean up the mess...
http://med.stanford.edu/ism/2011/april/engleman.html



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Natural sources:


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References:

In Parkinson's Disease, Brain Cells Abandon Mitochondria
ScienceDaily (Oct. 8, 2010) — In a study that sheds new light on the causes of Parkinson's disease, researchers report that brain cells in Parkinson's patients abandon their energy-producing machinery, the mitochondria. A shutdown in fuel can have devastating effects on brain cells, which consume roughly 20 percent of the body's energy despite making up only 2 percent of body weight... researchers, now show that a root cause of Parkinson's disease may lie in 10 gene sets related to energy production that spur neurons in the brain to "divorce" their mitochondria and related energy-producing pathways..."The most exciting result from our study for me is the discovery of PGC-1alpha as a new therapeutic target for early intervention in Parkinson's disease. PGC-1alpha is a master switch that activates hundreds of mitochondrial genes, including many of those needed to maintain and repair the power plants in the mitochondria,"... FDA-approved medications [Actos, CoQ10] that activate that PGC-1alpha are already available for widespread diseases like diabetes. These medications may jumpstart the development of new Parkinson's drugs; instead of having to start from scratch, pharmaceutical companies may be able to dust off their drug libraries and find look-alike drugs capable of targeting PGC-1alpha in the brain. "As we wrap up our first year of publishing the journal, the new study from Zheng et al. exemplifies the goal of Science Translational Medicine, applying knowledge and technology from different fields-such as neuroscience, genomics and bioinformatics-to achieve new discoveries,"...
http://www.sciencedaily.com/releases/2010/10/101006151557.htm


Study Dusts Sugar Coating Off Little-Known Regulation in Cells
ScienceDaily (Apr. 16, 2012) — In Alzheimer's disease, brain neurons become clogged with tangled proteins. Scientists suspect these tangles arise partly due to malfunctions in a little-known regulatory system within cells. Now, researchers have dramatically increased what they know about this particular regulatory system in mice. Such information will help scientists better understand Alzheimer's and other diseases in humans and could eventually provide new targets for therapies... The O-GlcNAc system likely adds another layer of control to the proteins that serve as a brain cell's widgets and gears -- control that might be muddled in Alzheimer's brains known to have problems in sugar metabolism...
http://www.sciencedaily.com/releases/2012/04/120416154048.htm

Tandem mass spectrometry identifies many mouse brain O-GlcNAcylated proteins including EGF domain-specific O-GlcNAc transferase targets.
Alfaro JF, Gong CX, Monroe ME, Aldrich JT, Clauss TR, Purvine SO, Wang Z, Camp DG 2nd, Shabanowitz J, Stanley P, Hart GW, Hunt DF, Yang F, Smith RD.
Proc Natl Acad Sci U S A. 2012 May 8;109(19):7280-5. Epub 2012 Apr 19.
Source:  Pacific Northwest National Laboratory, Richland, WA 99352, USA.
PMID:     22517741     [PubMed]  PMCID:     PMC3358849    [Available on 2012/11/8]
http://www.ncbi.nlm.nih.gov/pubmed/22517741

Alzheimer’s Disease Linked to Diabetes, Study Suggests
ScienceDaily (July 18, 2012)
…Previous research indicated that insulin plays an important role in the formation of memories. Once attached to neurons, oligomers cause insulin receptors to be eliminated from the surface membranes, contributing to insulin resistance in the brain. This launches a vicious cycle in which diabetes induces oligomer accumulation which makes neurons even more insulin resistant…
http://www.sciencedaily.com/releases/2012/07/120718164604.htm
http://www.umdnj.edu/cgi-bin/cgiwrap/hpappweb/newsroom.cgi?month=07&day=18&year=12&headline=Research+Identifies+Link+between+Alzheimer+s+Disease+and+Diabetes+

[This may mean that the “glucose hypometabolism” targeted by MCT oil (ketoacids) is due to oligomers, not mitochondrial dysfunction.]

Amyloid-β and Tau Pathology of Alzheimer's Disease Induced by Diabetes in an Animal Model.
Bitel CL, Kasinathan C, Kaswala RH, Klein WL, Frederikse PH.
J Alzheimers Dis. 2012 Jul 11. [Epub ahead of print]
Source:  Department of Pharmacology and Physiology and Rutgers-UMDNJ Integrative Neurosciences Program, UMDNJ-New Jersey Medical School, Newark, NJ, USA.
Abstract
Alzheimer's disease (AD) is the major age-dependent disease of the brain, but what instigates late-onset AD is not yet clear. Epidemiological, animal model, and cell biology findings suggest links between AD and diabetes. Although AD pathology is accelerated by diabetes in mice engineered to accumulate human-sequence amyloid-β (Aβ) peptides, they do not adequately model non-inherited AD. We investigated AD-type pathology induced solely by diabetes in genetically unmodified rabbits which generate human-sequence Aβ peptides. After 15 weeks, alloxan-treated diabetic rabbits with expected high blood glucose showed ∼5-fold increase in Aβ40/Aβ42 in cortex and hippocampus, and significantly, generated Aβ-derived assemblies found in human AD. Deposits of these putative pathogenic toxins were detected by Aβ/Aβ oligomer antibodies in brain parenchyma and surrounding vasculature, also co-localizing with markedly elevated levels of RAGE. Soluble brain extracts showed diabetes-induced buildup of Aβ oligomers on dot-blots. Phospho-tau also was clearly elevated, overlapping with βIII-tubulin along neuronal tracts. Indications of retina involvement in AD led to examination of AD-type pathology in diabetic retinas and showed Aβ accumulation in ganglion and inner nuclear cell layers using Aβ/oligomer antibodies, and RAGE again was elevated. Our study identifies emergence of AD pathology in brain and retina as a major consequence of diabetes; implicating dysfunctional insulin signaling in late-onset AD, and a potential relationship between Aβ-derived neurotoxins and retinal degeneration in aging and diabetes, as well as AD. AD-type pathology demonstrated in genetically unmodified rabbits calls attention to the considerable potential of the model for investigations of AD pathogenesis, diagnostics, and therapeutics.
PMID: 22785400 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/22785400

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Updated: July 2, 2012
Inception: July 2, 2012