Open AccessCentral insulin‐like growth factor‐1 ( IGF ‐1) restores whole‐body insulin action in a model of age‐related insulin resistance and IGF ‐1 decline
Author(s) -
Huffman Derek M.,
Farias Quipildor Gabriela,
Mao Kai,
Zhang Xueying,
Wan Junxiang,
Apontes Pasha,
Cohen Pinchas,
Barzilai Nir
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12415
Subject(s) - insulin , endocrinology , medicine , insulin resistance , hyperinsulinemia , biology , insulin like growth factor , growth factor , insulin receptor , receptor
Summary 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.