Broadening the definition of brain insulin resistance in aging and Alzheimer's disease.

Broadening the definition of brain insulin resistance in aging and Alzheimer's disease. Exp Neurol. 2018 Dec 18;313:79-87 Authors: Frazier HN, Ghoweri AO, Anderson KL, Lin RL, Porter NM, Thibault O Abstract It has been >20 years since studies first revealed that the brain is insulin sensitive, highlighted by the expression of insulin receptors in neurons and glia, the presence of circulating brain insulin, and even localized insulin production. Following these discoveries, evidence of decreased brain insulin receptor number and function was reported in both clinical samples and animal models of aging and Alzheimer's disease, setting the stage for the hypothesis that neuronal insulin resistance may underlie memory loss in these conditions. The development of therapeutic insulin delivery to the brain using intranasal insulin administration has been shown to improve aspects of memory or learning in both humans and animal models. However, whether this approach functions by compensating for poorly signaling insulin receptors, for reduced insulin levels in the brain, or for reduced trafficking of insulin into the brain remains unclear. Direct measures of insulin's impact on cellular physiology and metabolism in the brain have been sparse in models of Alzheimer's disease, and even fewer studies have analyzed these processes in the aged brain. Nevertheless, recent evidence supports the role of brain insulin as a mediator of glucose meta...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research