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However, when IGFBP-1 levels are chronically lowered during prolonged intra-portal hyperinsulinemia (e.g., obesity, Cushing’s syndrome and glucocorticoid therapy), the “accelerator” effect of IGFBP-1 is at play to increase serum free IGF-I (35, 40)

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These questions point the way forward for both basic research and future clinical trials