Insulin, Insulin-like Growth Factor-1 and Neurodegeneration: A Perspective on Parvaneh Tafreshi et al (2010)

Abstract

The role of insulin and insulin growth factor-1 (IGF-1) in the brain has been extensively revaluated in the last two decades. Several previous studies have shown that insulin is involved in a number of neurotrophic, neuromodulatory, and/or neuroendocrine effects, including the appetite control and energy expenditure and the interaction between insulin resistance, diabetes, and amyloid deposition in Alzheimer’s disease (1, 2). Insulin acts as a growth factor in the brain, providing a neuroprotective action by activating dendritic sprouting, regeneration and stem cell proliferation (3). Together with other peptides, like ghrelin or cholecystokinin, insulin is involved in the complex neuropeptidergic signaling network in the hypothalamus which regulates anabolic and catabolic balance (4). In general, insulin serves as a systemic feedback signal to reduce appetite and is therefore involved in body weight regulation and eating behavior. Insulin receptors in the brain are expressed at high levels in neurons, and to a lesser extent in glia and other areas of the brain (5). Impairment of insulin signaling in the brain has been linked to neurodegenerative diseases. Several rodent model studies of diet-induced obesity, using high-fat diet and/or fructose, found that insulin resistance leads to cognitive impairment as well as altered eating behavior (6-9). Moreover, mice with neuron-specific insulin receptor deletion show an increase in food uptake and body weight (10). On the other hand, restoration of insulin receptors in the brain of mice with tissue-restricted insulin receptor expression maintains energy homeostasis and prevents diabetes (11). In addition, patients with type 2 diabetes (T2D) have an increased risk of developing Alzheimer’s disease (AD) (1, 12), since insulin resistance can promote the production and secretion of amyloid s-peptide, a hallmark of AD (13). Impairment of insulin signaling in the brain has also been shown to be a factor in central nervous system dysfunctions such as Huntington’s disease or parkinsonism (14, 15). Therefore, the increased risk of cognitive dysfunction in elderly diabetic patients is probably a consequence of the synergistic interaction between diabetes-related metabolic derangements and the structural and functional cerebral changes due to normal aging processes (16, 17). A recent study published in 2010 by Tafreshi et al. (18), showed increased levels of IGF-1 protein in the brain of insulin-resistant rats compared to healthy controls. The study investigated the expression of IGF-1 protein in different areas of the brain including the brain stem, cerCopyright c 2011 Kowsar M. P. Co. All rights reserved.