IGF-I
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Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
similar in
molecular structure Molecular geometry is the three-dimensional arrangement of the atoms that constitute a molecule. It includes the general shape of the molecule as well as bond lengths, bond angles, torsional angles and any other geometrical parameters that deter ...
to
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
which plays an important role in childhood growth, and has
anabolic Anabolism () is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breaking ...
effects in adults. IGF-1 is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''IGF1''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. IGF-1 consists of 70
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s in a single chain with three intramolecular disulfide bridges. IGF-1 has a molecular weight of 7,649 Daltons. In dogs, an ancient mutation in IGF1 is the primary cause of the
toy A toy or plaything is an object that is used primarily to provide entertainment. Simple examples include toy blocks, board games, and dolls. Toys are often designed for use by children, although many are designed specifically for adults and pet ...
phenotype. IGF-1 is produced primarily by the
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
. Production is stimulated by
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
(GH). Most of IGF-1 is bound to one of 6 binding proteins (IGF-BP). IGFBP-1 is regulated by insulin. IGF-1 is produced throughout life; the highest rates of IGF-1 production occur during the pubertal growth spurt. The lowest levels occur in infancy and old age. A synthetic analog of IGF-1,
mecasermin Mecasermin, sold under the brand name Increlex, also known as recombinant human insulin-like growth factor-1 (rhIGF-1), is a recombinant form of human insulin-like growth factor 1 (IGF-I) which is used in the long-term treatment of growth failure ...
, is used in children for the treatment of growth failure. Cyclic glycine-proline (cGP) is metabolite of hormone Insulin-like Growth Factor-1 (IGF-1). It has a cyclic structure, lipophilic nature, and is enzymatically stable which makes its a more favourable candidate for manipulating the binding-release process between IGF-1 and its binding protein thereby, normalising IGF-1 function.


Synthesis and circulation

IGF-1 is produced primarily by the
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
as an endocrine hormone as well as in target tissues in a paracrine/autocrine fashion. Production is stimulated by
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
(GH) and can be retarded by
undernutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...
, growth hormone insensitivity, lack of
growth hormone receptor Growth hormone receptor is a protein that in humans is encoded by the ''GHR'' gene. GHR orthologs have been identified in most mammals. Structure Growth hormone receptor (GHR) is a transmembrane protein consisting of 620 amino acids. The recep ...
s, or failures of the downstream signaling pathway post GH receptor including
SHP2 Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology region 2 domain-containing phosphatase-2 (SHP-2), or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in huma ...
and STAT5B. Approximately 98% of IGF-1 is always bound to one of 6 binding proteins (IGF-BP).
IGFBP-3 Insulin-like growth factor-binding protein 3, also known as IGFBP-3, is a protein that in humans is encoded by the ''IGFBP3'' gene. IGFBP-3 is one of six IGF binding proteins ( IGFBP-1 to IGFBP-6) that have highly conserved structures and bind th ...
, the most abundant protein, accounts for 80% of all IGF binding. IGF-1 binds to IGFBP-3 in a 1:1 molar ratio. IGFBP-1 is regulated by insulin. IGF-1 is produced throughout life. The highest rates of IGF-1 production occur during the pubertal growth spurt. The lowest levels occur in infancy and old age. Protein intake increases IGF-1 levels in humans, independent of total calorie consumption. Factors that are known to cause variation in the levels of
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
(GH) and IGF-1 in the circulation include: insulin levels, genetic make-up, the time of day, age, sex, exercise status, stress levels, nutrition level and body mass index (BMI), disease state, ethnicity, estrogen status and
xenobiotic A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...
intake.


Mechanism of action

IGF-1 is a primary mediator of the effects of
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
(GH). Growth hormone is made in the
anterior pituitary A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...
gland, is released into the blood stream, and then stimulates the
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
to produce IGF-1. IGF-1 then stimulates systemic body growth, and has growth-promoting effects on almost every
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
in the body, especially skeletal
muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
,
cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...
,
bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
,
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
,
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
,
nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
,
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
,
hematopoietic Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...
, and
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
cells. In addition to the
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
-like effects, IGF-1 can also regulate cellular DNA synthesis. IGF-1 binds to at least two cell surface
receptor tyrosine kinase Receptor tyrosine kinases (RTKs) are the high- affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kin ...
s: the
IGF-1 receptor The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 ( IGF-1) and by a related hormone called IGF-2. ...
(IGF1R), and the
insulin receptor The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. Metabolically, the insulin receptor plays a key role in the regulation of glucose ho ...
. Its primary action is mediated by binding to its specific receptor, IGF1R, which is present on the surface of many cell types in many tissues. Binding to the IGF1R initiates intracellular signaling. IGF-1 is one of the most potent natural activators of the
AKT Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, tran ...
signaling pathway In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
, a stimulator of cell growth and proliferation, and a potent inhibitor of
programmed cell death Programmed cell death (PCD; sometimes referred to as cellular suicide) is the death of a cell (biology), cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers ...
. The IGF-1 receptor seems to be the "physiologic" receptor because it binds IGF-1 with significantly higher affinity than insulin receptor does. IGF-1 activates the insulin receptor at approximately 0.1 times the potency of insulin. Part of this signaling may be via IGF1R/Insulin Receptor heterodimers (the reason for the confusion is that binding studies show that IGF1 binds the insulin receptor 100-fold less well than insulin, yet that does not correlate with the actual potency of IGF1 in vivo at inducing phosphorylation of the insulin receptor, and hypoglycemia). IGF-1 binds and activates its own receptor,
IGF-1R The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 ( IGF-1) and by a related hormone called IGF-2. ...
, through the cell surface expression of Receptor Tyrosine Kinase's (RTK's) and further signal through multiple intracellular transduction cascades. IGF-1R is the critical role-playing inducer in modulating the metabolic effects of IGF-1 for cellular senescence and survival. At a localized target cell, IGF-1R elicits the mediation of paracrine activity. After its activation the initiation of intracellular signaling occurs inducing a magnitude of signaling pathways. An important mechanistic pathway involved in mediating a cascade affect a key pathway regulated by phosphatidylinositol-3 kinase (
PI3K Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ...
) and its downstream partner, mTOR (mammalian Target of Rapamycin). Rapamycin binds with the enzyme FKBPP12 to inhibit the mTORC1 complex. mTORC2 remains unaffected and responds by up-regulating AKT, driving signals through the inhibited mTORC1. Phosphorylation of Eukaryotic translation initiation factor 4E (
EIF4E Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein that in humans is encoded by the ''EIF4E'' gene. Structure and function Most eukaryotic cellular mRNAs are blocked at their 5'-ends with the 7-methyl-guanosine fi ...
) by mTOR suppresses the capacity of Eukaryotic translation initiation factor 4E-binding protein 1 (
EIF4EBP1 Eukaryotic translation initiation factor 4E-binding protein 1 (also known as 4E-BP1) is a protein that in humans is encoded by the ''EIF4EBP1'' gene. Function This gene encodes one member of a family of translation repressor proteins. The prot ...
) to inhibit EIF4E and slow metabolism. A mutation in the signaling pathway PI3K-AKT-mTOR is a big factor in the formation of tumors found predominantly on skin, internal organs, and secondary lymph nodes (Kaposi sarcoma). IGF-1R allows the activation of these signaling pathways and subsequently regulates the cellular longevity and metabolic re-uptake of biogenic substances. A therapeutic approach targeting towards the reduction of such tumor collections could be induced by ganitumab. Ganitumab is a monoclonal antibody (mAb) directed antagonistically against IGF-1R. Ganitumab binds to IGF-1R, preventing binding of IGF-1 and the subsequent triggering of the PI3K-mTOR signaling pathway; inhibition of this pro-survival pathway may result in the inhibition of tumor cell expansion and the induction of tumor cell apoptosis. Insulin-like growth factor 1 has been shown to bind and interact with all seven IGF-1 binding proteins (IGFBPs):
IGFBP1 Insulin-like growth factor-binding protein 1 (IBP-1) also known as placental protein 12 (PP12) is a protein that in humans is encoded by the ''IGFBP1'' gene. Function This gene is a member of the Insulin-like growth factor-binding protein (IGFB ...
,
IGFBP2 Insulin-like growth factor-binding protein 2 is a protein that in humans is encoded by the ''IGFBP2'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." mean ...
,
IGFBP3 Insulin-like growth factor-binding protein 3, also known as IGFBP-3, is a protein that in humans is encoded by the ''IGFBP3'' gene. IGFBP-3 is one of six IGF binding proteins ( IGFBP-1 to IGFBP-6) that have highly conserved structures and bind the ...
,
IGFBP4 Insulin-like growth factor-binding protein 4 is a protein that in humans is encoded by the ''IGFBP4'' gene. Function This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP do ...
,
IGFBP5 Insulin-like growth factor-binding protein 5 (IBF-5) is a protein that in humans is encoded by the ''IGFBP5'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity.. ...
,
IGFBP6 Insulin-like growth factor-binding protein 6 (IGFBP-6) is a protein that in humans is encoded by the ''IGFBP6'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity ...
, and
IGFBP7 Insulin-like growth factor-binding protein 7 is a protein that in humans is encoded by the ''IGFBP7'' gene. The major function of the protein is the regulation of availability of insulin-like growth factors (IGFs) in tissue as well as in modulati ...
. Some IGFBPs are inhibitory. For example, both IGFBP-2 and IGFBP-5 bind IGF-1 at a higher affinity than it binds its receptor. Therefore, increases in serum levels of these two IGFBPs result in a decrease in IGF-1 activity.


Metabolic effects

As a major growth factor, IGF-1 is responsible for stimulating growth of all cell types and causing significant metabolic effects. One important metabolic effect of IGF-1 is its ability to signal cells that sufficient nutrients are available for cells to undergo hypertrophy and cell division. These signals also enable IGF-1 to inhibit cell apoptosis and increase the production of cellular proteins. IGF-1 receptors are ubiquitous, which allows for metabolic changes caused by IGF-1 to occur in all cell types. IGF-1's metabolic effects are far-reaching and can coordinate protein, carbohydrate, and fat metabolism in a variety of different cell types. The regulation of IGF-1's metabolic effects on target tissues is also coordinated with other hormones such as growth hormone and insulin.


Related growth factors

IGF-1 is closely related to a second protein called "
IGF-2 Insulin-like growth factor 2 (IGF-2) is one of three protein hormones that share structural similarity to insulin. The MeSH definition reads: "A well-characterized neutral peptide believed to be secreted by the liver and to circulate in the blo ...
". IGF-2 also binds the IGF-1 receptor. However, IGF-2 alone binds a receptor called the "IGF-2 receptor" (also called the mannose-6 phosphate receptor). The insulin-like growth factor-II receptor (IGF2R) lacks signal transduction capacity, and its main role is to act as a sink for IGF-2 and make less IGF-2 available for binding with IGF-1R. As the name "insulin-like growth factor 1" implies, IGF-1 is structurally related to insulin, and is even capable of binding the insulin receptor, albeit at lower affinity than insulin. A
splice variant Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be in ...
of IGF-1 sharing an identical mature region, but with a different E domain is known as ''mechano-growth factor'' (MGF).


Disorders


Laron dwarfism

Rare diseases characterized by inability to make or respond to IGF-1 produce a distinctive type of growth failure. One such disorder, termed
Laron dwarfism Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency (GHRD), is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 (IGF-1; somatomedin) production in response t ...
does not respond at all to
growth hormone treatment Growth hormone therapy refers to the use of growth hormone (GH) as a prescription medication—it is one form of hormone therapy. Growth hormone is a peptide hormone secreted by the pituitary gland that stimulates growth and cell reproduction. ...
due to a lack of GH receptors. The FDA has grouped these diseases into a disorder called severe primary IGF deficiency. Patients with severe primary IGFD typically present with normal to high GH levels, height below 3 standard deviations (SD), and IGF-1 levels below 3 SD. Severe primary IGFD includes patients with mutations in the GH receptor, post-receptor mutations or IGF mutations, as previously described. As a result, these patients cannot be expected to respond to GH treatment. People with Laron syndrome have very low rates of cancer and
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
. Notably people with untreated Laron syndrome also never develop acne.


Acromegaly

Acromegaly is a
syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek σύνδρομον, meaning "concurrence". When a syndrome is paired ...
that results when the
anterior pituitary A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...
gland produces excess
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
(GH). A number of disorders may increase the pituitary's GH output, although most commonly it involves a tumor called
pituitary adenoma Pituitary adenomas are tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas.somatotroph Somatotropes (from the Greek ''sōmat'' meaning "body" and ''tropikós'' meaning "of or pertaining to a turn or change") are cells in the anterior pituitary that produce growth hormone. Structure Somatotropic cells constitute about 30−40% of a ...
s). It leads to anatomical changes and metabolic dysfunction caused by both an elevated GH and elevated IGF-1 levels. High level of IGF-1 in acromegaly is related to an increased risk of some cancers, particularly colon cancer and thyroid cancer.


Cancer

A mutation in the signaling pathway PI3K-AKT-mTOR is a factor in the formation of
tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
found predominantly on skin, internal organs, and secondary lymph nodes (Kaposi sarcoma). IGF-1R allows the activation of these signaling pathways and subsequently regulates the cellular longevity and metabolic re-uptake of biogenic substances. A therapeutic approach targeting towards the reduction of such tumor collections could be induced by
ganitumab Ganitumab is a human monoclonal antibody against type 1 insulin-like growth factor receptor ( IGF1R), designed for the treatment of cancers. Ganitumab was developed by Amgen Amgen Inc. (formerly Applied Molecular Genetics Inc.) is an America ...
. Ganitumab is a monoclonal antibody (mAb) directed antagonistically against IGF-1R. Ganitumab binds to IGF-1R, preventing binding of IGF-1 and the subsequent triggering of the PI3K-mTOR signaling pathway; inhibition of this pro-survival pathway may result in the inhibition of tumor cell expansion and the induction of tumor cell apoptosis.


Use as a diagnostic test

IGF-1 levels can be measured in the blood in 10-1000 ng/ml amounts. As levels do not fluctuate greatly throughout the day for an individual person, IGF-1 is used by physicians as a
screening test Screening, in medicine, is a strategy used to look for as-yet-unrecognised conditions or risk markers. This testing can be applied to individuals or to a whole population. The people tested may not exhibit any signs or symptoms of a disease, or t ...
for
growth hormone deficiency Growth hormone deficiency (GHD), or human growth hormone deficiency, is a medical condition resulting from not enough growth hormone (GH). Generally the most noticeable symptom is that an individual attains a short height. Newborns may also prese ...
and excess in acromegaly and
gigantism Gigantism ( el, γίγας, ''gígas'', "giant", plural γίγαντες, ''gígantes''), also known as giantism, is a condition characterized by excessive growth and height significantly above average. In humans, this condition is caused by ove ...
. Interpretation of IGF-1 levels is complicated by the wide normal ranges, and marked variations by age, sex, and pubertal stage. Clinically significant conditions and changes may be masked by the wide normal ranges. Sequential measurement over time is often useful for the management of several types of pituitary disease, undernutrition, and growth problems.


Causes of elevated IGF-1 levels

* acromegaly (especially when GH is also high) *
high-protein diet A high-protein diet is a diet in which 20% or more of the total daily calories comes from protein.Longe, Jacqueline L. (2008). ''High-protein diet''. In ''The Gale Encyclopedia of Diets: A Guide to Health and Nutrition''. Gale. pp. 524-526. Most ...
*high glycemic-index diet *
dairy product Dairy products or milk products, also known as lacticinia, are food products made from (or containing) milk. The most common dairy animals are cow, water buffalo, nanny goat, and ewe. Dairy products include common grocery store food items in th ...
s (except for cheese) consumption *
delayed puberty Delayed puberty is when a person lacks or has incomplete development of specific sexual characteristics past the usual age of onset of puberty. The person may have no physical or hormonal signs that puberty has begun. In the United States, girls ar ...
*
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
*
hyperthyroidism Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...
* IGF-1 assay problems * some rare tumors (i.e.
carcinoid A carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) ...
s) secreting IGF-1


Use as a therapeutic agent

Patients with severe primary insulin-like growth factor-1 deficiency (IGFD), called
Laron syndrome Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency (GHRD), is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 (IGF-1; somatomedin) production in response t ...
, may be treated with either IGF-1 alone or in combination with
IGFBP-3 Insulin-like growth factor-binding protein 3, also known as IGFBP-3, is a protein that in humans is encoded by the ''IGFBP3'' gene. IGFBP-3 is one of six IGF binding proteins ( IGFBP-1 to IGFBP-6) that have highly conserved structures and bind th ...
.
Mecasermin Mecasermin, sold under the brand name Increlex, also known as recombinant human insulin-like growth factor-1 (rhIGF-1), is a recombinant form of human insulin-like growth factor 1 (IGF-I) which is used in the long-term treatment of growth failure ...
(brand name Increlex) is a synthetic analog of IGF-1 which is approved for the treatment of growth failure. IGF-1 has been manufactured recombinantly on a large scale using both yeast and ''E. coli''. IGF-1 may have a beneficial effect on atherosclerosis and cardiovascular disease. IGF-1 has also been shown to have an antidepressant effect in mouse models.


Clinical trials


Recombinant protein

Several companies have evaluated administering recombinant IGF-1 in clinical trials for
type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar ...
,
type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...
,
amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
, severe burn injury and myotonic muscular dystrophy. Results of clinical trials evaluating the efficacy of IGF-1 in type 1 diabetes and type 2 diabetes showed reduction in hemoglobin A1C levels and daily insulin consumption. However the sponsor discontinued the program due to an exacerbation of
diabetic retinopathy Diabetic retinopathy (also known as diabetic eye disease), is a medical condition in which damage occurs to the retina due to diabetes mellitus. It is a leading cause of blindness in developed countries. Diabetic retinopathy affects up to 80 perc ...
, coupled with a shift in corporate focus towards
oncology Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ó ...
. Two clinical studies of IGF-1 for ALS were conducted and although one study demonstrated efficacy the second was equivocal, and the product was not submitted for approval to the FDA.


Society and culture


History of name

In the 1950s IGF-1 was called "
sulfation Sulfation is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected less directly. Regardless of the mechanism, the ...
factor" because it stimulated sulfation of cartilage in vitro, and in the 1970s due to its effects it was termed "nonsuppressible insulin-like activity" (NSILA).


See also

*
Somatopause Somatopause is the progressive decline in the levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), hormones of the hypothalamic–pituitary–somatotropic axis (HPS axis), with age. Secretion of GH may only be 60% of that of a yo ...


References


External links

* * {{DEFAULTSORT:Insulin-Like Growth Factor 1 Peptide hormones Growth factors Hormones of the somatotropic axis Insulin-like growth factor receptor agonists Insulin receptor agonists Aging-related proteins Neurotrophic factors Developmental neuroscience World Anti-Doping Agency prohibited substances