Scientific evidence indicates that higher levels of blood glucose in the brain, due to the inability of the brain to process the glucose (impaired fasting glucose metabolism) is strongly linked to cognitive decline including brain shrinkage and dementia including Alzheimer's Disease (AD). Neurons in the brain must have a continuous supply of glucose, which is utilized as their primary energy source. Transport of glucose into the neuron is through the glucose transport proteins GLUT1 and GLUT3 which are not dependent on insulin. Since the brain is so dependent on GLUT1 and GLUT3 to sustain energy for the function of the neurons, any loss of GLUT functioning results in the death of neurons. Furthermore. the higher levels of uncontrolled glucose causes destructive pathological changes to the brain associated with Alzheimer's Disease. The impaired ability of the brain to properly metabolize glucose is often referred to as "type 3 diabetes". (1-6)
HYPERGLYCEMIA (Including High-Normal Glucose Levels). Dysregulation of glucose homeostasis leads to higher levels of glucose in brain tissue including brain shrinkage, and the formation of brain pathologies such as beta amyloid plaques and fibrils. Higher blood sugar levels (including high normal, prediabetes and type 2 diabetes) begin with insulin resistance, whereby blood glucose cannot be adequately absorbed by the cells, and glucose levels in the blood stream increase.
Higher plasma glucose levels is correlated to increases in brain glucose. Furthermore, this continues to be exacerbated when GLUT1 and GLUT3 transporters are decreased in function and/or number, and glucose is unable to reach the neurons. GLUT transporters are affected by glycation in diabetics, and may render the transport mechanism non-functional. Higher glucose levels correlate to the most severe loss of brain function in Alzheimer's Disease. (11)
Classifications of fasting blood glucose levels:
AMYLOID PLAQUES AND TAU FIBRIL ENTANGLEMENTS
Impaired glucose metabolism in brain tissue, including reduced levels of GLUT1 and GLUT3, are significantly linked to amyloid plaque accumulation and brain tau fibril entanglements.
Pathological changes in the brain linked to high blood glucose:
GLUCOSE TRANSPORTERS - Impact on Brain Glucose Metabolism
Natural Support for Glucose Homeostasis
YELLOW LONGEVITY (Yellow Glucose Homeostasis)
MEMORY ACTION (Andrographolide, more)
(1) An Y, et al, Evidence for brain glucose dysregulation in Alzheimer's disease. Alzheimers Dement. 2017 Oct 19
(2) Cherbuin N, et al. Higher normal fasting plasma glucose is associated with hippocampal atrophy: The PATH Study. Neurology. 2012 Sep
(3) Mortby ME, et al, High "normal" blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through life study. PLoS One. 2013 Sep
(4) Porter-Turner MM, et al. Relationship between erythrocyte GLUT1 function and membrane glycation in type 2 diabetes. Br J Biomed Sci. 2011
(5) Barros LF, et al. Near-critical GLUT1 and Neurodegeneration. J Neurosci Res. 2017 Nov
(7) Guo C, et al. Chronic hyperglycemia induced via the heterozygous knockout of Pdx1 worsens neuropathological lesion in an Alzheimer mouse model. Sci Rep. 2016 Jul
(8) Ying Liu, et al. Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer disease. J Neurochem 2009 Oct.
(9) Liu F, et al. Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer's disease. Brain. 2009.
(10) Gong CX, et al. O-GlcNAcylation: A regulator of tau pathology and neurodegeneration. Alzheimers Dement. 2016 Oct;
(11) Mittal K, et al. Shared links between type 2 diabetes mellitus and Alzheimer's disease: A review. Diabetes Metab Syndr. 2016 Apr-Jun
(12) Zhang, C, et a. Antihyperglycaemic and organic protective effects on pancreas, liver and kidney by polysaccharides from Hericium erinaceus SG-02 in streptozotocin-induced diabetic mice. Scientific Reports 7, Article number: 10847 (2017)
(13) Cai H, et al. Lycium barbarum L. Polysaccharide (LBP) Reduces Glucose Uptake via Down-Regulation of SGLT-1 in Caco2 Cell. Molecules. 2017 Feb.
(14) Naik RR, et al. Andrographolide reorganise hyperglycaemia and distorted antioxidant profile in streptozotocin-induced diabetic rats. Cardiovasc Hematol Agents Med Chem. 2017 Oct
(15) Zhao Y, et al. Preventive effects of jujube polysaccharides on fructose-induced insulin resistance and dyslipidemia in mice. Food Funct. 2014 Aug
(16) Fang P, et al. Baicalin against obesity and insulin resistance through activation of AKT/AS160/GLUT4 pathway. Mol Cell Endocrinol. 2017 Jun
(17) Wan CP, et al. [Piperine regulates glucose metabolism disorder in HepG2 cells of insulin resistance models via targeting upstream target of AMPK signaling pathway]. Zhongguo Zhong Yao Za Zhi, 2017 Feb
(18) O'Neill HM. AMPK and Exercise: Glucose Uptake and Insulin Sensitivity. Diabetes Metab J. 2013 Feb
(19) Kim KJ, et al, Fucoidan regulate blood glucose homeostasis in C57BL/KSJ m+/+db and C57BL/KSJ db/db mice. Fitoweapia. 2012 Sep
(20) Yu W, wt al. Fucoidan ameliorates pancreatic β-cell death and impaired insulin synthesis in streptozotocin-treated β cells and mice via a Sirt-1-dependent manner. Mol Butr Food Res. 2017 Oct;
(21) de Las Heras N, et al. Molecular factors involved in the hypolipidemic- and insulin-sensitizing effects of a ginger (Zingiber officinale Roscoe) extract in rats fed a high-fat diet. Appl Physiol Nutr Metab. 2017 Feb
(22) Bumke-Vogt C, et al. The flavones apigenin and luteolin induce FOXO1 translocation but inhibit gluconeogenic and lipogenic gene expression in human cells. PLoS One. 2014 Aug
(23) Zhao NJ, et al. Curcumin suppresses Notch‑1 signaling: Improvements in fatty liver and insulin resistance in rats. Mol Med Rep. 2018 Jan;