Central insulin‐like growth factor‐1 ( IGF ‐1) restores whole‐body insulin action in a model of age‐related insulin resistance and IGF ‐1 decline
Year: 2015
Type: article
Abstract: Low insulin-like growth factor-1 (IGF-1) signaling is associated with improved longevity, but is paradoxically linked with several age-related diseases in humans. Insulin-like growth factor-1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF-1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole-body insulin action in aging. Utilizing hyperinsulinemic-euglycemic clamps, we show that old insulin-resistant rats with age-related declines in IGF-1 level demonstrate markedly improved whole-body insulin action, when treated with central IGF-1, as compared to central vehicle or insulin (P < 0.05). Furthermore, central IGF-1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P < 0.05). Taken together, IGF-1 action in the brain and periphery provides a 'balance' between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at 'tipping the balance' of IGF-1 action centrally are the optimal approach to achieve healthy aging and longevity in humans.
Source: Aging Cell
DOI: 10.1111/acel.12415
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,790
Funders: Glenn Foundation for Medical Research, Fondation pour la Recherche Médicale, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences
Awards: Dietary Restriction, GH/IGF-l & Mechanisms of Cellular Protection and Regeneration, G2399858043, Excess nutrients and the metabolic syndrome of aging, Peripheral and central IGF-1 action in energy balance and longevity modulation , Clinical and Translational Science Award, Einstein's Nathan Shock Center of Excellence in Basic Biology of Aging, Dysregulation of Glucose Homeostasis in Aging, Plasma Mitochondrial Peptide Assays as Biomarkers of Environmental Toxin Exposure, G7304749776, Peripheral and central IGF-1 action in energy balance and longevity modulation , Novel Mitochondrially Encoded Peptides and Their Role in Health and Disease, G7640403211, LGP/Longenity, New York Obesity Research Center, Cancer Center Support Grant, Training in Aging Research, NYR-Diabetes Research Center (NYR-DRC)
OpenAlex ID: W2102207014