What is the role of Insulin-like Growth Factor-1 (IGF-1) in the body?

What IGF-1 Does in the Body

IGF-1 (Insulin-like Growth Factor-1) is a critical anabolic hormone that stimulates cell growth, proliferation, and survival while also regulating glucose metabolism, with its primary physiological role being mediation of growth hormone effects throughout the body. 1

Primary Physiological Functions

Growth and Development

• IGF-1 acts through transmembrane IGF-1 receptors to initiate glucose uptake and stimulate cell growth and proliferation 1
• It serves as the principal mediator of growth hormone (GH), playing a crucial role in promoting cell growth and differentiation during childhood while maintaining anabolic effects in adults 2, 3
• Approximately 75% of circulating IGF-1 originates from the liver in response to growth hormone stimulation 4

Metabolic Effects

• IGF-1 has insulin-like effects that reduce blood glucose levels, contrasting with growth hormone which causes insulin resistance 3
• It regulates carbohydrate, lipid, and protein metabolism through tyrosine-kinase-linked receptor pathways 3
• IGF-1 has been used experimentally to treat both type 1 and type 2 diabetes due to its glucose-lowering properties 3

Cellular Mechanisms

• IGF-1 exerts potent anti-apoptotic and pro-survival effects on both normal and transformed cells 4, 5
• It functions through the MAPK and PI3K signaling pathways after binding to IGF-1 receptors 5
• IGF-1 can migrate to the cell nucleus where it functions as a transcriptional activator 5

Tissue-Specific Actions

Cardiac Function

• IGF-1 is a major regulator of "adaptive" or "physiological" cardiac hypertrophy and promotes survival of cardiac myocytes 1
• Cardiac fibroblasts serve as an important source of IGF-1 production in the heart 1
• Growth hormone and IGF-1 are physiological modulators of myocardial structure and function, with GH activating cardiac cell growth through IGF-1-mediated mechanisms 6

Bone and Periodontal Tissue

• IGF-1 is a bone trophic factor that enhances proliferation of periodontal ligament cells and bone precursor cells 1
• It demonstrates synergistic effects with PDGF-BB on mitogenesis of periodontal and bone precursor cells 1, 6
• IGF-1 administration increases bone formation markers in patients with anorexia nervosa 6

Neural Tissue

• IGF-1 enhances proliferation and reduces apoptosis in neural progenitor cells during differentiation 7
• It plays a crucial role in neural stem cell isolation and differentiation into neuronal lineages 7

Bioavailability and Regulation

Binding Proteins

• Approximately 98% of all circulating IGF-1 is bound to six insulin-like growth factor binding proteins (IGFBPs) 2
• IGFBPs serve as carrier proteins and regulate IGF-1 bioavailability by binding it with affinity equal to or greater than the IGF-1 receptor 2
• Ten IGFBP-related proteins (IGFBP-rPs) also bind IGF-1, albeit with lower affinities 2

Production Sites

• IGF-1 is produced by virtually all tissues and acts in endocrine, autocrine, and paracrine fashion 4
• The liver produces the majority of endocrine IGF-1, while local tissues produce IGF-1 for autocrine/paracrine effects 6

Clinical Implications Related to Morbidity and Mortality

Longevity and Aging

• Reduced IGF-1 signaling is associated with increased lifespan and reduced risk of aging-related diseases 1
• Continuous stimulation of the IGF-1 pathway leads to higher risk of aging-related diseases through reduced autophagy, increased inflammation, and mitochondrial dysfunction 1
• Laron dwarves with reduced IGF-1 levels show major reductions in risk of type 2 diabetes and cancer despite being overweight 1

Disease States

• People with acromegaly (elevated GH and IGF-1) have a two- to threefold increase in mortality, primarily from vascular disease 1
• Chronic excess IGF-1 secretion results in biventricular cardiac hypertrophy and can progress to dilated cardiomyopathy 6
• Polymorphic variants causing reduced IGF-1 signaling confer health and lifespan benefits in humans, with female Ashkenazi Jewish centenarians showing overrepresentation of loss-of-function mutations in the IGF-1 receptor 1

Cancer Risk

• IGF-1 has emerged as a significant factor in oncology due to its potent anti-apoptotic and pro-survival roles 5
• It is expressed in almost all types of cancer and has become a molecular target in oncology 5
• The IGF-1 signaling pathway in hepatocellular carcinoma can be targeted by inhibiting the intracellular tyrosine kinase 1

Common Pitfalls

• Oral estrogen suppresses hepatic IGF-1 production through first-pass liver metabolism, which is particularly problematic in amenorrheic athletes who already have low endogenous IGF-1 concentrations 6
• Growth hormone therapy to increase IGF-1 is expensive and associated with undesirable side effects including salt and water retention and impaired glucose metabolism 6
• The existence of IGFBPs significantly reduces levels of immunoreactive IGF-1 in samples, requiring multiple pre-treatment steps that reduce reproducibility and complicate interpretation of IGF-1 assay results 2