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

The Role of Insulin-like Growth Factor-1 (IGF-1) in the Body

IGF-1 is a crucial peptide hormone that functions as the principal mediator of growth hormone, promoting cell growth, differentiation, and survival while playing essential roles in metabolism, bone health, cardiovascular function, and immune regulation throughout the lifespan.

Primary Functions of IGF-1

IGF-1 serves multiple vital physiological functions:

• Growth and Development

  • Mediates most growth-promoting effects of growth hormone (GH) 1
  • Stimulates cell proliferation and differentiation in various tissues 2
  • Critical for normal childhood growth and continues to have anabolic effects in adults 2

• Metabolic Regulation

  • Promotes glucose uptake in cells 3
  • Influences insulin sensitivity and glucose homeostasis
  • Acts as a nutrient sensor, signaling the availability of nutrients needed for anabolic actions 4

• Tissue-Specific Effects

  • Cardiac Function: Regulates "adaptive" or "physiological" cardiac hypertrophy and promotes survival of cardiac cells in response to cytotoxic interventions 3
  • Bone Health: Essential for bone formation and maintenance, with low levels associated with decreased bone mineral density 3, 5
  • Muscle: Promotes protein synthesis and muscle growth
  • Immune System: Involved in regulation of immunity and inflammation 6

Regulation of IGF-1

IGF-1 production and bioavailability are regulated through several mechanisms:

• Production: Primarily produced by the liver (75%) in response to GH, but also produced locally in peripheral tissues including growth plates 1, 7

• Bioavailability:

  • Approximately 98% of circulating IGF-1 is bound to insulin-like growth factor binding proteins (IGFBPs) 2
  • Six IGFBPs and ten IGFBP-related proteins regulate IGF-1 bioavailability 2
  • Only free IGF-1 (1-2%) is biologically active 2

• Nutritional Status:

  • IGF-1 levels fall during malnutrition and respond promptly to refeeding 4
  • Low energy availability significantly reduces IGF-1 production 3, 5
  • IGF-1 serves as a nutritional biomarker in clinical settings 4

Clinical Significance of IGF-1

IGF-1 has important implications in various clinical contexts:

• Diagnostic Marker:

  • Used to diagnose growth hormone deficiency 1
  • Monitors GH replacement therapy 1
  • Serves as a nutritional biomarker in malnutrition states 4

• Female Athlete Triad:

  • Low IGF-1 is part of the Female Athlete Triad syndrome 3, 5
  • Recovery of energy status and IGF-1 levels precedes recovery of menstrual status and bone mineral density 5

• Cardiovascular Health:

  • Regulates adaptive cardiac hypertrophy 3
  • Abnormal IGF-1 levels are associated with cardiovascular disease risk 3

• Therapeutic Applications:

  • Recombinant human IGF-1 (rhIGF-1) has been used to increase bone formation markers in conditions like anorexia nervosa 3
  • Combined with estrogen therapy, rhIGF-1 has shown significant increases in bone mineral density 3

Pathological Implications

Dysregulation of IGF-1 is associated with various pathological conditions:

• Low IGF-1 States:

  • Malnutrition and low energy availability 5, 4
  • Growth hormone deficiency 1
  • Hypothyroidism 5
  • Inflammatory conditions (acute phase response) 4, 6

• Elevated IGF-1 States:

  • Acromegaly (increased mortality from vascular disease) 3
  • Potential role in cancer development and progression 3

Clinical Management of IGF-1 Abnormalities

For low IGF-1 levels, management should target the underlying cause:

• Nutritional Interventions:

  • Increase caloric intake by 20-30% over baseline energy needs 5
  • Target energy availability ≥45 kcal/kg of fat-free mass 5
  • Consider nutritional consultation for persistent deficiencies 5

• Hormone Replacement:

  • Consider GH replacement therapy based on clinical presentation and severity of deficiency 5
  • Address other hormonal deficiencies that may affect IGF-1 levels 5

Important Considerations

• IGF-1 levels should be interpreted with caution as they are influenced by many factors beyond nutritional status, including the acute phase response and endocrine conditions 4

• Regular monitoring of IGF-1 levels is recommended to assess treatment efficacy in relevant conditions 5

• IGF-1 is also a potential doping agent in sports due to its anabolic effects 2

• The insulin/insulin-like growth factor signaling pathway (IIS pathway) is one of the most well-known pathways implicated in the aging process, with reduced signaling associated with increased lifespan in various models 3

Understanding the multifaceted roles of IGF-1 in the body provides valuable insights into growth, metabolism, and various pathological conditions, making it an important biomarker and therapeutic target in clinical practice.