Location: Diet, Genomics and Immunology Lab
Title: Polyphenols, Insulin Sensitivity, and the Brain Authors
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: June 1, 2009
Publication Date: N/A
Technical Abstract: We have isolated water-soluble polyphenols found in cinnamon that are multifunctional and improve insulin sensitivity, glucose uptake, and have antioxidant and anti-inflammatory properties in experimental animals and humans. These compounds may also be potentially neuroprotective as oxidative stress, abnormalities in glucose utilization, and inflammation, are also all implicated in neurological disorders. Abnormalities in insulin signaling in the brain can contribute to Alzheimer’s disease (AD) and AD has recently been called “type 3 diabetes” due to the observation that abnormalities in insulin signaling in the brain associated with AD are similar to those observed in insulin sensitive tissues of people with type 2 diabetes. Neuropathologically, AD is characterized by the deposition of extracellular plaques, composed principally of amyloid ß protein, and intracellularly of neurofibrillary tangles, generally associated with hyperphosphorylated tau. Polyphenols from cinnamon inhibit both tau aggregation and amyloid ß filament formation. Oxidative stress and mitochondrial dysfunction are key events implicated in both neuronal and astrocytic dysfunction/death and cinnamon and tea polyphenols, as well as insulin, protect neuronal death in cultures from Aß toxicity. Mitochondrial dysfunction in neurons from Aß toxicity is also protected by these polyphenols. Ischemic stroke is caused by an interruption of cerebral blood flow, which can lead to vascular leakage, inflammation, tissue injury, and necrosis. Polyphenols from cinnamon and tea have neuroprotective effects in PC12 neuronal cells subjected to oxygen-glucose deprivation. One neuroprotective mechanism of such polyphenols may be due to their effects on improving mitochondrial membrane potential/mitochondrial function. Glial swelling, a key feature of cytotoxic edema, due to oxygen-glucose deprivation, is also prevented by cinnamon and tea polyphenols in C6 glial cells. In addition, green tea epigallocatechin-3-gallate improves insulin sensitivity, reduces beta-amyloid levels and plaques and delays memory regression in mice. In summary, in vitro studies demonstrate that cinnamon and tea polyphenols not only improve insulin sensitivity but also protect neuronal and glial cells from ischemic injury and amyloid ß toxicity. Animal studies demonstrate that tea polyphenols reverse or alleviate signs and symptoms of Alzheimer’s disease and premature losses in memory regression. Human studies demonstrate that increased intake of cinnamon and tea polyphenols leads to improved insulin sensitivity and related pathologies associated with aging.