title: 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.
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.
authors.affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.|Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Derek M
authors.initials: DM
authors.lastname: Huffman
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.|Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Farias Quipildor
authors.affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.|Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Mao
authors.affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.|Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang, Beijing, 100101, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90089, USA.
authors.forename: Junxiang
authors.initials: J
authors.lastname: Wan
authors.affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.|Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Pasha
authors.initials: P
authors.lastname: Apontes
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90089, USA.
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.|Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.|Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
mesh_terms: D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique / Q000379:methods; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007328:Insulin; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I; D005947:Glucose
keywords: aging; animal models; central nervous system; endocrinology; glucose metabolism; insulin resistance; insulin-like growth factor