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 |
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| Authors: | Derek M Huffman Gabriela Farias Quipildor Kai Mao Xueying Zhang Junxiang Wan Pasha Apontes Pinchas Cohen Nir Barzilai |
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| Affiliation: | 1. Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA;2. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA;3. Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA;4. Institute of Zoology, Chinese Academy of Sciences, Beijing, China;5. Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA;6. Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA |
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| 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. |
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| Keywords: | aging central nervous system endocrinology glucose metabolism insulin resistance insulin‐like growth factor animal models |
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