title: The pancreas-brain axis: insight into disrupted mechanisms associating type 2 diabetes and Alzheimer's disease.
abstract: Epidemiological and observational studies indicate a positive correlation between type 2 diabetes (T2DM) and dementia, with an increased risk of dementia and Alzheimer's disease (AD) associated with insulin-treated diabetes patients. The purpose of this review is to reveal the molecular mechanisms that connect physiological and pathological processes commonly observed in T2DM and AD. Conformational modifications in peptide residues, such as amyloid-β peptide in AD and amylin in T2DM have been shown to instigate formation of insoluble protein aggregates that get deposited in extracellular spaces of brain and pancreatic tissue thus disrupting their normal function. Impaired insulin signaling plays a critical role in AD pathogenesis by reducing IRS-associated PI3 kinase activity and increasing GSK-3β activity. GSK-3β has been suggested to be a component of the γ-secretase complex and is involved in amyloid-β protein precursor processing. GSK-3β along with CDK5 is responsible for hyperphosphorylation of tau leading to the formation of neurofibrillary tangles. In summary, there is evidence to believe that a molecular link connects AD and T2DM and has potential for further investigation toward development of an effective therapeutic target.
authors.affiliation: Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL, USA.
authors.forename: Gauri S
authors.initials: GS
authors.lastname: Desai
authors.affiliation: Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, Auburn University at Montgomery, Montgomery, AL, USA.
authors.forename: Thangiah
authors.initials: T
authors.lastname: Geetha
authors.affiliation: Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL, USA.
authors.forename: Suresh T
authors.initials: ST
authors.lastname: Mathews
authors.affiliation: Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL, USA.
authors.forename: B Douglas
authors.initials: BD
authors.lastname: White
authors.affiliation: Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Huggins
authors.affiliation: Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL, USA.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Zizza
authors.affiliation: Department of Physiology, Laboratory of Diabetes and Exercise Metabolism, Midwestern University, Glendale, AZ, USA.
authors.forename: Tom L
authors.initials: TL
authors.lastname: Broderick
authors.affiliation: Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL, USA.
authors.forename: Jeganathan Ramesh
authors.initials: JR
authors.lastname: Babu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides; D001921:Brain / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D010179:Pancreas / Q000378:metabolism*; D011972:Receptor, Insulin; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D011972:Receptor, Insulin
keywords: Alzheimer's disease; amyloid-β; insulin receptor; neurofibrillary tangle; type 2 diabetes