ISSN: 0034-8376
eISSN: 2564-8896
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Abstract

The Role of Insulin Resistance and Glucose Metabolism Dysregulation in the Development of Alzheimer´s Disease

VOLUME 68 - NUMBER 2 / March - April (Review Articles)

Isabel Arrieta-Cruz, Department of Basic Research, National Institute of Geriatrics, Mexico City, Mexico
Roger Gutiérrez-Juárez, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA

Alzheimer´s disease is a chronic neurodegenerative disorder affecting millions of people worldwide, characterized by a progressive decline in cognitive functions. Factors involved in the pathogenesis of Alzheimer´s disease include metabolic alterations such as insulin resistance and hyperglycemia, both of which are also hallmarks of type-2 diabetes mellitus. The accumulation of β-amyloid peptides in the brain of Alzheimer´s patients is responsible in part for the neurotoxicity underlying the loss of synaptic plasticity that triggers a cascade of events leading to cell death. A large number of studies revealed the key role of the hippocampus and cerebral cortex in the memory and learning deficits of Alzheimer´s disease. Although ample evidence suggests a link between altered insulin action, the dysregulation of glucose metabolism, and β-amyloid accumulation in animal models and humans with Alzheimer´s, no supporting evidence was available. In this article, we review the potential toxic effects of β-amyloid in the hypothalamus, a brain center involved in the control of insulin action and glucose metabolism. Furthermore, we discuss our recent studies unraveling a novel neurotoxic action of β-amyloid that perturbs hypothalamic glucoregulation, leading to increased hepatic glucose production and hyperglycemia. These findings provide evidence for a link between β-amyloid toxicity and altered glucose metabolism.

Keywords: Alzheimer´s. Diabetes. Amyloid peptide. Glucose metabolism. Insulin resistance. Hypothalamus. Liver.

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