Opposing Metabolic Effects of Growth Hormone and Insulin-like Growth Factor I: Review and Clinical Implications

Abstract

The growth hormone (GH) and insulin-like growth factor I (IGF-I) axis is fundamental to growth and metabolism, yet the distinct and often opposing metabolic actions of these 2 hormones are not always appreciated in clinical practice, necessitating a comprehensive synthesis of current evidence. Understanding this dichotomy is essential for optimizing therapeutic strategies in endocrine and metabolic disorders, where hormone modulation carries both benefits and risks. This review starts by examining the molecular mechanisms of GH and IGF-I signaling, including receptor activation and downstream pathways such as Janus kinase 2- signal transducer and activator of transcription (JAK2-STAT) and Phosphoinositide 3-kinase-protein kinase B (PI3K-AKT). It then explores the physiological roles of each hormone, highlighting GH’s direct catabolic effects on glucose and lipid metabolism and IGF-I’s insulin-sensitizing and anabolic properties. The tissue-specific actions of GH and IGF-I in the liver, adipose tissue, skeletal muscle, and pancreas are discussed to illustrate their divergent metabolic targeting. The integrated regulation of the GH-IGF-I axis by factors such as exercise, nutrition, and feedback inhibition is also addressed. Finally, the review overviews evidence from recent clinical studies examining GH and IGF-I in conditions including type 2 diabetes, GH deficiency, and acromegaly, and considers the therapeutic implications of their opposing effects. Future research should focus on the precise molecular determinants of tissue-specific hormone sensitivity to enable more targeted interventions. Combination therapies and personalized medicine approaches, guided by genetic and metabolic profiling, hold particular promise for harnessing the beneficial effects of GH and IGF-I while mitigating their respective adverse metabolic consequences.