What is the metabolic function of Insulin-like Growth Factor 1 (IGF-1)?

From the Guidelines

Insulin-like Growth Factor 1 (IGF-1) primarily functions as a mediator of growth hormone effects, regulating metabolism by promoting anabolic processes and inhibiting catabolic ones, as evidenced by its role in diagnosing GH excess in children and adolescents 1.

Metabolic Functions of IGF-1

The metabolic functions of IGF-1 are multifaceted, including:

• Stimulating protein synthesis in muscles and other tissues by activating the PI3K/Akt/mTOR pathway, which increases amino acid uptake and enhances translation of proteins.
• Regulating carbohydrate metabolism by promoting glucose uptake into cells, particularly in muscle and fat tissue, through increased translocation of GLUT4 transporters to cell membranes, similar to the action of insulin.
• Enhancing glycolysis and glycogen synthesis while suppressing gluconeogenesis in the liver, as supported by the correlation between serum IGF1 levels and GH levels in diagnosing GH excess 1.
• Promoting lipogenesis and inhibiting lipolysis, contributing to fat storage, which is relevant in the context of GH excess and associated metabolic complications.
• Stimulating bone growth and mineralization by enhancing osteoblast activity and collagen production, which is crucial for the diagnosis and management of GH excess in children and adolescents, as outlined in the consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence 1.

Clinical Relevance of IGF-1

In clinical practice, IGF-1 levels are used as a reliable marker for GH excess, but their interpretation requires consideration of age-adjusted, sex-adjusted, and Tanner stage-matched normal ranges, as well as potential confounding factors such as hypothyroidism, malnutrition, or diabetes mellitus 1. The metabolic effects of IGF-1 are mediated through IGF-1 receptors found throughout the body, activating multiple downstream signaling cascades that regulate cell growth, proliferation, differentiation, and survival while preventing apoptosis. Therefore, accurate interpretation of IGF-1 levels is essential for the diagnosis and management of GH excess, taking into account the complex interplay between IGF-1, GH, and other metabolic factors 1.

From the Research

Metabolic Function of IGF-1

The metabolic function of Insulin-like Growth Factor 1 (IGF-1) is multifaceted, playing a crucial role in various physiological processes. Some of the key aspects of IGF-1's metabolic function include:

• Stimulation of protein synthesis in muscle 2
• Stimulation of free fatty acid use 2
• Improvement in glycemic control in patients with extreme insulin resistance 2
• Enhancement of insulin sensitivity in Type 1 and Type 2 diabetes 2
• Induction of glucose transport activity, glucose transporter gene expression, DNA-synthesis, and expression of proto-oncogene c-fos in 3T3-L1 adipocytes 3
• Regulation of glucose metabolism and metabolic pathways 4

Role in Metabolic Diseases

IGF-1 has been implicated in the prevention and treatment of metabolic diseases, including:

• Metabolic syndrome X (MSx) 4
• Type 1 and Type 2 diabetes 2, 5
• Insulin resistance 2, 5
• Cardiovascular disease 5

Mechanism of Action

The mechanism of action of IGF-1 involves:

• Binding to its own receptor, which is highly specific and distinct from the insulin receptor 3
• Stimulation of metabolic and mitogenic responses in various cell types, including 3T3-L1 adipocytes 3
• Coordination with growth hormone and insulin actions to regulate intermediary metabolism 2