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

^*Rhea Rony Mathew
Medicine, St Martinus University, Willemstad, Curaçao, Netherlands
Chinmai Purana Matha
Medicine, Ramaiah Medical College, Bengaluru, Karnataka, India
Kakumani Hari Chandana
Medicine, Sri Padmavati Medical College For Women, Tirupati, Andhra Pradesh, India

^*Corresponding Author:

Rhea Rony Mathew
Medicine, St Martinus University, Willemstad, Curaçao, Netherlands

Published on: 2026-10-16

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.

Keywords

Diabetes mellitus, Growth hormone, Insulin resistance, Insulin-like growth factor I, Metabolic syndrome, Type 2 diabetes

Introduction

GH and IGF-I are central components of the endocrine system that regulate growth and metabolism [1-10]. GH, secreted by the anterior pituitary, exerts its effects both directly and indirectly through the stimulation of IGF-I production primarily in the liver and other tissues [11]. IGF-I, in turn, mediates many of the anabolic and growthpromoting actions attributed to GH, functioning as a key effector molecule in the GH/IGF-I axis [11]. Despite their interconnected roles, GH and IGF-I exhibit distinct and sometimes opposing effects on various metabolic processes, a phenomenon that has been recognized and studied extensively over the years [11]. The complex interplay between these hormones is fundamental to understanding normal physiology and the pathophysiology of metabolic disorders, making their study a cornerstone of endocrinology research [12].

The metabolic effects of GH and IGF-I are of significant clinical interest due to their implications in health and disease. GH influences glucose, lipid, and protein metabolism, often promoting lipolysis and gluconeogenesis, which can lead to insulin resistance if dysregulated [11]. Conversely, IGF-I generally exerts insulin-like effects, promoting glucose uptake and anabolic processes [13]. Recognizing the opposing nature of these hormones’ actions is crucial for developing targeted therapies for conditions such as GH deficiency, acromegaly, diabetes, and metabolic syndrome [2]. Furthermore, understanding their divergent effects aids clinicians in balancing therapeutic benefits against potential risks, such as hyperglycemia or dyslipidemia, associated with hormone supplementation or suppression [14]. As research advances, elucidating these mechanisms remains vital for optimizing treatment strategies and improving patient outcomes [11].

This review aims to overview current literature on the opposing metabolic effects of GH and IGF-I, highlighting their distinct mechanisms of action and physiological roles. By comparing their impacts on key metabolic pathways—particularly glucose, lipid, and protein metabolism—the review aims to clarify how these hormones influence overall metabolic homeostasis. Additionally, it discusses the clinical implications of their divergent actions, including considerations for managing metabolic disorders and hormone-related diseases. Ultimately, the review endeavors to provide a comprehensive understanding that can inform future research directions and therapeutic approaches targeting the GH/IGF-I axis [11].