Insulin-Like Growth Factor-I

IGF-I is the main mediator of GH's growth promoting effect, known as "growth mediator". GH is secreted by the pituitary gland, which stimulates liver cells to synthesize and release IGF-I. IGF-I in the circulation further acts on target tissues such as bones, muscles, and organs, completing the transmission and execution of growth signals.
Bone growth: IGF-I directly activates the proliferation and differentiation of epiphyseal chondrocytes, promotes longitudinal extension of long bone growth plates, and is a key driving factor for height growth in children; Simultaneously stimulating osteoblast activity, increasing bone density, inhibiting osteoclast bone resorption, and maintaining adult bone homeostasis.

Muscle development: promotes the proliferation and differentiation of skeletal muscle satellite cells (muscle stem cells), accelerates muscle fiber hypertrophy; Upregulate amino acid transport and protein synthesis, inhibit muscle protein degradation, and improve muscle quality and strength.
Organ development: Promote cell proliferation and functional maturation of internal organs such as the heart, liver, kidneys, and lungs, ensuring normal development of fetal and childhood organs.

IGF-I has insulin-like activity (intensity about 1/60 of insulin) and regulates fat metabolism, serving as a key link between growth and metabolism.
Blood glucose regulation: promotes the uptake and utilization of glucose by skeletal muscle and adipose tissue, accelerates glycogen synthesis; Inhibit hepatic gluconeogenesis, reduce hepatic glucose output, improve insulin sensitivity, and assist in maintaining blood glucose stability.

Fat metabolism: promotes fat breakdown and reduces fat accumulation; Inhibiting the proliferation and differentiation of adipocytes, reducing body fat percentage, especially reducing visceral fat deposition, and lowering the risk of metabolic syndrome.
Energy balance: regulates the hypothalamic appetite center and affects feeding behavior; Optimize energy metabolism efficiency by regulating mitochondrial function in cells.

IGF-I regulates the cell cycle, promotes proliferation and differentiation, inhibits apoptosis, and maintains stable tissue cell numbers by activating core signaling pathways such as PI3K/Akt and MAPK/ERK.
Cell proliferation: stimulates cell division in tissues such as the skin, gastrointestinal mucosa, and vascular endothelium, promoting tissue growth and renewal.

Anti apoptosis: Upregulate the expression of anti apoptotic protein (Bcl-2), downregulate the activity of pro apoptotic protein (Bax), reduce cell apoptosis induced by oxidative stress, inflammation, ischemia and other injuries, and protect tissue integrity.
Differentiation regulation: Inducing stem cells to differentiate into specific cell types such as muscles, nerves, and bones, and participating in tissue repair and regeneration.

Insulin-Like Growth Factor-I is a neurotrophic factor that plays an irreplaceable role in the development, repair, and functional regulation of the central and peripheral nervous systems.
Neurodevelopment: promotes the proliferation, migration, and differentiation of embryonic neurons, induces the formation and connection of neural synapses, and constructs neural networks; Accelerate the maturation of oligodendrocytes, promote myelin synthesis, and ensure efficient transmission of neural signals.

Neuroprotection: Inhibit neuronal apoptosis, alleviate oxidative stress, glutamate toxicity, and inflammation damage to neurons; Promote cerebral blood flow, improve nutrient supply to brain tissue, and protect against ischemic and hypoxic brain injury.
Cognitive function: Enhance the plasticity of hippocampal neurons, promote the expression of learning and memory related genes, and improve cognitive ability; Delaying the progression of neurodegenerative diseases such as senile dementia and Parkinson's disease.

Children with GHD have reduced hepatic IGF-I synthesis due to insufficient pituitary GH secretion, resulting in growth retardation, short stature, and delayed bone age.
Diagnostic value: Decreased serum IGF-I levels are the core biochemical indicators of GHD, and combined with GH stimulation test can improve diagnostic accuracy.
Alternative therapy: Recombinant human IGF-I (rhIGF-I) can directly promote bone growth and improve height prognosis in children with GH insensitive syndrome (Laron syndrome) and GHD who are unresponsive to rhGH treatment.

Children with ISS who do not have GH deficiency but have low serum IGF-I levels or insufficient biological activity are common causes of short stature in children.
Diagnostic and therapeutic value: Detecting IGF-I levels can assist in determining the etiology of ISS; RhIGF-I treatment can significantly improve the growth rate of pediatric patients and increase adult height.

Adult AGHD is often caused by pituitary tumors, pituitary surgery, or radiation therapy, and is characterized by muscle loss, fat accumulation, osteoporosis, fatigue, and cognitive decline. The core pathology is a decrease in IGF-I levels.
Diagnosis and monitoring: Serum IGF-I is the preferred indicator for AGHD screening and efficacy monitoring, with significantly reduced levels supporting diagnosis.
Alternative therapy: rhGH replacement therapy can increase muscle mass, reduce visceral fat, improve bone density, and enhance quality of life by increasing IGF-I levels.

The core of osteoporosis is reduced bone formation and increased bone resorption. IGF-I, as a key regulatory factor of bone metabolism, decreases with age and is closely related to the onset of osteoporosis.
Pathogenesis association: Reduced IGF-I leads to decreased osteoblast activity, overactivation of osteoclasts, decreased bone density, and increased risk of fractures.
Therapeutic potential: rhIGF-I combined with calcium supplements and vitamin D can promote bone formation, increase bone density, and reduce the risk of vertebral and non vertebral fractures, especially for elderly osteoporosis.

The level of IGF-I in brain tissue of AD patients is significantly reduced, which is associated with neuronal apoptosis, synaptic loss, and cognitive decline.
Therapeutic research: Exogenous IGF-I can reduce - amyloid deposition, inhibit Tau protein hyperphosphorylation, alleviate neuroinflammation, and improve learning and memory abilities, making it a potential therapeutic target for AD.

The apoptosis of dopaminergic neurons in the substantia nigra of PD is related to insufficient IGF-I, which can protect dopaminergic neurons and promote nerve repair.

Clinical exploration: IGF-I treatment can delay the decline of PD motor function, improve symptoms such as tremors and muscle rigidity, and combined with levodopa can enhance the efficacy.

Upregulation of IGF-I expression after cerebral ischemia is an endogenous neuroprotective mechanism; Exogenous supplementation can alleviate brain edema, inhibit neuronal apoptosis, promote angiogenesis and nerve regeneration, and improve neurological deficits.

Patients with metabolic syndrome (obesity, hypertension, hyperglycemia, hyperlipidemia) often have decreased levels of IGF-I and insulin resistance, and IGF-I is involved in the occurrence and development of glucose and lipid metabolism disorders.
Pathological mechanism: Insufficient IGF-I leads to decreased insulin sensitivity and increased blood glucose levels; Reduced fat breakdown, accumulation of visceral fat, and exacerbation of metabolic disorders.
Intervention value: Increasing IGF-I level can improve insulin resistance, reduce blood sugar and visceral fat, providing a new intervention direction for metabolic syndrome and type 2 diabetes.

The high metabolic state of the body after burns leads to a decrease in IGF-I levels, delayed skin healing, and increased risk of infection.
Therapeutic application: Local or systemic application of rhIGF-I can promote the proliferation of skin fibroblasts, collagen synthesis, accelerate wound healing, and reduce scar formation.

Long term bed rest, surgical immobilization, elderly frailty, tumor cachexia, etc. lead to a decrease in IGF-I levels, greater muscle protein breakdown than synthesis, reduced muscle mass, and decreased muscle strength.
Intervention effect: IGF-I can reverse muscle atrophy, increase muscle mass and strength, improve limb function, and enhance the self-care ability of elderly patients with frailty.

Abnormal activation of the IGF-I signaling pathway is closely related to the occurrence, invasion, and metastasis of various tumors, and elevated serum IGF-I levels are tumor risk markers.
Auxiliary diagnosis: The serum IGF-I level of lung cancer, breast cancer, prostate cancer, colorectal cancer and other patients has significantly increased, which can be used as an auxiliary indicator for tumor screening.

Prognostic assessment: High IGF-I levels indicate high malignancy, high risk of metastasis, and poor prognosis of the tumor.
Therapeutic targets: Inhibiting the IGF-I/IGF-1R signaling pathway (such as IGF-1R monoclonal antibodies) can block tumor cell proliferation and induce apoptosis, making it an important direction for targeted cancer therapy.