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Insulin-like growth factor 1 (IGF-1) and long chain IGF (Ir3igf-1)

July 18, 2019

Properties and mechanism of action

Insulin-like growth factor 1 (IGF-1, hIGF-1, or somatomedin C) is a polypeptide hormone occurring in the body, composed of 70 amino acids. It mediates a number of the anabolic (i.e. tissue growth-stimulating) effects of the growth hormone. IGF-1 production in the liver is stimulated by the growth hormone, but IGF-1 is also produced in other tissues, such as muscle tissue [1].

Long chain IGF (LR3IGF-1, IGF-1 LR3, arginine IGF, or long chain arginine IGF) is an IGF derivative used for research purposes. The changes made to the LR3IGF-1 molecule result in LR3IGF-1, which in comparison with IGF-1 is physiologically stronger with effects that last longer.

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. The chemical structure and effects of mecasermin are identical with physiological IGF-1.

Physiological IGF-1 is the principal hormonal mediator of height growth. The growth hormone secreted by the human pituitary gland binds to its receptors in the liver and other tissues and stimulates the synthesis and secretion of hIGF-1.

In target tissue, IGF-1 activates the homologous IGF-1 receptor, which leads to intracellular signalling and activates a number of processes leading to height growth. It also causes bone, muscle, and other tissue growth. The IGF-1 signalling pathways are among the most important and most researched anabolic stimuli inducing muscle hypertrophy. In addition to the anabolic effect, IGF-1 is known to increase glycogen and collagen synthesis and it may indirectly increase lipolysis induced by the growth hormone [1, 2, 3].

The metabolic effects of IGF-1 further the uptake of glucose, fatty acids and amino acids in such a way that the metabolism supports the growth of tissues, such as muscles.

Medical use

In Finland, rhIGF-1 is used for the long-term treatment of dysplasia in children and youth who have severe IGF-1 deficiency. In addition to dysplasia treatment, rhIGF-1 is also being researched for use in the treatment of anorexia, as well as the severe insulin resistance associated with diabetes.

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

In the case of dysplasia, the rhIGF-1 treatment may continue even for several years. The preparation should not be used on patients, whose epiphyseal disks are closed, meaning that height growth has stopped.

Use

IGF-1 and LR3IGF-1 are classified as doping substances in the Finnish Criminal Code. Thus far, scientific studies have mentioned IGF abuse only sporadically, but it is known that athletes and muscle builders have abused IGF-1. Their purpose of use is to grow muscle mass, get fat to burn faster than usual, and accelerate recovery from injuries [4]. IGF-1 is often used to enhance the anabolic effects of the growth hormone and anabolic steroids [2]. IGF-1 is thought to be beneficial to virility, stamina, immunity and bone density as well [4].

By contrast with anabolic steroids, IGF-1 is used in standard doses without breaks while rhIGF-1 strengthens the muscle-growing effects of the growth hormone and anabolic steroids.

Adverse effects

Little information is available on the risks of long-term IGF-1 doping. IGF-1 doping is quite recent and the doses used are higher than the doses used in the field of medicine [5]. The risks of the adverse effects of IGF-1 grow if the growth hormone is used concurrently, as is quite often the case.

Not all of the adverse effects of LR3IGF-1 on humans have been identified, but presumably they are similar to those of ordinary IGF-1.

Moderate doses of IGF-1 cause adverse effects less often and the decline in blood sugar can be reduced by combining IGF-1 uptake with meals. The risk of harm often grows when the doses exceed 60–80 µg/kg/24 hrs [6].

RhIGF-1 may cause hypoglycemia in the same way that insulin does, meaning that it decreases the blood sugar content [7, 8, 9]. The use of rhIGF-1 in clinical doses causes hypoglycemia for almost 50% of the patients. Hypoglycemia caused by overdoses 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 include allergic reactions, swellings, headaches, convulsions, nausea, increasing intracranial pressure, the increased growth of malignant tumours and the excessive growth of the cardiac muscle, the liver, and the kidneys [2, 4, 5, 7, 10].

Long-term overdoses of rhIGF-1 can cause acromegaly (i.e. the excessive growth of the cartilages, the forehead, the nose, the chin, the hands and the feet), cardiac muscle changes, and arrhythmias.

RhIGF-1 and LR3iIGF do not cause disturbances in the sex hormone function.

 

Timo Seppälä
Medical Director
Finnish Center for Integrity in Sports FINCIS (previously the Finnish Antidoping Agency FINADA)

Updated by
Dopinglinkki

 

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[2] Anderson LJ, Tamayose JM, Garcia JM. Use of growth hormone, IGF-1 and insulin for anabolic purpose: Pharmacological basis, methods of detection and adverse effects. Mol Cell Endorcinol. 2017: S0303–7207(17)30337–4

[3] Dunkel L. 2010. Kasvuhormoni – kasvurustojärjestelmä. In Dunkel L. Sane T, Välimäki M. Endokrinologia. Duodecim. (2nd edition)

[4] Guha N, Cowan D, Sönksen P, Holt R. Insulin-like growth factor-I (IGF-1) misuse in athletes and potential methods for detection. Anal Bioanal Chem. 2013;405(30):9669–83

[5] Spaziani S, Imperlini E, Mancini A, Caterino M, Buono P, Orrù S. Insulin-like growth factor 1 receptor signaling induced by supraphysiological blood lymphocytes. Proteomics. 2014;14(13–14):1623–9

[6] Aguirre G, Rodríguez De Ita J, de la Garza R, Castilla-Cortazar I. Insulin-like growth factor-1 deficiency and metabolic syndrome. J Transl Med. 2016; 14:3

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

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

[9] Göke & Fehmann. 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. 1996; 93–106

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



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