Insulin-like growth factor (IGF-1)

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Insulin-like growth factor (IGF-1)

Properties and mechanism of action

IGF-1 (hIGF-1, insulin-like growth factor-1, somatomedin C) is a polypeptide hormone that exist in the body and is composed of 70 amino acids. It mediates several anabolic (growth-stimulating) effects on tissue by growth hormones.

IGF-1 (rhIGF-1) that is manufactured for medical use by recombinant DNA-technology is called mecasermin. It is made in Escherichia coli bacteria to which the human IGF-1 gene is carried. Its chemical structure and effects are identical with physiological IGF-1.

Physiological IGF-1 is the principal hormonal mediator of statural growth. In humans, the pituitary gland secreted growth hormone binds to its receptors in the liver and other tissues and stimulates the synthesis and secretion of hIGF-1. 

In target tissue, the type 1 IGF-1 receptor, which is homologous to the insulin receptor, is activated by IGF-1, leading to intracellular signaling that stimulates multiple processes leading to statural growth. It also causes the growth of bones, muscles and other tissues.

The metabolic activities of hIGF-1 improve the uptake of glucose, fatty acids and amino acids into cells such that the metabolism supports the growth of tissues, for example muscles.

Medical use

RhIGF-1 is used for long-term treatment of growth disturbances in children and youth who have severe IGF-1 deficiency. RhIGF-1 is also being researched for use in anorexia treatment, in addition to growth disturbances, and for treatment of severe insulin resistance.

According to the condition of use stated by Fimea, treatment must be given under the supervision of doctors who are specifically experienced in the diagnostics and treatment of patients that suffer from growth disturbances. It is recommended that an ultrasound image of the patient’s heart be taken before the rhIGF-1 treatment.

The rhIGF-1 treatment for growth disturbances may continue for many years. The preparation should not be used with patients whose epiphyseal disks are closed meaning that statural growth has stopped.

Abuse

IGF-1 is classified as a doping substance in the Penal Code. Up until now, there has been only rare mention about the abuse of IGF-1 in scientific studies but it is known that sport athletes and muscle builders abuse IGF-1. Their purpose of use is to enhance the growth of muscle mass, to increase the burning of fat and to speed up recovery after injuries [1].

The use of IGF-1 differs from anabolic steroids in that it is used in standard doses and there are no pauses in use. RhIGF-1 improves the muscle-growth stimulating effects of growth hormones and anabolic steroids.

Adverse effects

RhIGF-1 may cause hypoglycemia in the same way that insulin does, meaning that it decreases the sugar content in blood [2, 3, 4]. The use of rhIGF-1 in clinical doses causes hypoglycemia for almost half of the patients. Hypoglycemia caused by over-sized doses can lead to unconsciousness or even death. If rhIGF-1 is used together with insulin, the doses should be decreased because of the increased risk of hypoglycemia.

Other adverse effects caused by rhIGF-1 can be allergic reactions, headaches, cramps, nausea, increasing intracranial hypertension, increased growth of malignant tumors and excessive growth of heart muscle [2, 5].

Long-term use of rhIGF-1 with oversized doses can cause acromegaly (excessive growth of gristles, forehead, nose, chin, hands and foots) and heart muscle changes and arrhythmias. RhIGF-1 doesn’t cause disturbances in the activity of sex hormones.

Timo Seppälä
Medical Director
The Finnish Antidoping Agency FINADA

[1] Guha, Sönksen & Holt (2009): IGF-I abuse in sport: Current knowledge and future prospects for detection. Growth Hormone & IGF Research 19: 408–41.

[2] Clark (2004): Recombinant human insulin-like growth factor I (IGF-I): risks and benefits of normalizing blood IGF-I concentrations. Hormone Research 62 Suppl 1: 93–100.

[3] Dunger, Yuen & Ong (2004): Insulin-like growth factor I and impaired glucose tolerance. Hormone Research 62 Suppl 1: 101–7.

[4] Göke & Fehmann (1996): Insulin and insulin-like growth factor-I: their role as risk factors in the development of diabetic cardiovascular disease. Diabetes Research and Clinical Practice Suppl: 93–106.

[5] Yuen & Dunger (2007):Therapeutic aspects of growth hormone and insulin-like growth factor-I treatment on visceral fat and insulin sensitivity in adults. Diabetes, Obesity & Metabolism 9(1): 11–22.

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