Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

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 det ...

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

which plays an important role in childhood growth, and has

anabolic Anabolism () is the set of metabolic pathways that construct macromolecules like DNA or RNA from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catab ...

effects in adults. In the 1950s IGF-1 was called " sulfation 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). IGF-1 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''IGF1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. IGF-1 consists of 70

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s in a single chain with three intramolecular disulfide bridges. IGF-1 has a

molecular weight A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

of 7,649 daltons. In dogs, an ancient

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

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 p ...

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

. IGF-1 is produced primarily by the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

. Production is stimulated by growth hormone (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. Low IGF-1 levels are associated with

cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

, while high IGF-1 levels are associated with

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

. Mid-range IGF-1 levels are associated with the lowest mortality. A synthetic analog of IGF-1, mecasermin, is used for the treatment of growth failure in children with severe IGF-1 deficiency. Cyclic glycine-proline (cGP) is a metabolite of hormone insulin-like growth factor-1 (IGF-1). It has a cyclic structure, lipophilic nature, and is enzymatically stable which makes it 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

The polypeptide hormone IGF-1 is synthesized primarily in the

upon stimulation by growth hormone (GH). It is a key mediator of anabolic activities in numerous tissues and cells, such as growth hormone-stimulated growth,

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

and protein translation. Due to its participation in the GH-IGF-1 axis it contributes among other things to the maintenance of muscle strength, muscle mass, development of the skeleton and is a key factor in brain, eye and lung development during fetal development. Studies have shown the importance of the GH/IGF-1 axis in directing development and growth, where mice with a IGF-1 deficiency had a reduced body- and tissue mass. Mice with an excessive expression of IGF-1 had an increased mass. The levels of IGF-1 in the body vary throughout life, depending on age, where peaks of the hormone is generally observed during puberty and the postnatal period. After puberty, when entering the third decade of life, there is a rapid decrease in IGF-1 levels due to the actions of GH. Between the third and eighth decade of life, the IGF-1 levels decrease gradually, but unrelated to functional decline. However, protein intake is proven to increase IGF-1 levels.

Mechanism of action

IGF-1 is a primary mediator of the effects of growth hormone (GH). Growth hormone is made in the

anterior pituitary The anterior pituitary (also called the adenohypophysis or pars anterior) is a major Organ (anatomy), organ of the endocrine system. The anterior pituitary is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that t ...

gland, released into the bloodstream, and then stimulates the

to produce IGF-1. IGF-1 then stimulates systemic body growth, and has growth-promoting effects on almost every cell in the body, especially skeletal

muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

cartilage Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the Electrochemistry, electrochemical nerv ...

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 animal coverings, such as the arthropod exoskeleton, have different ...

hematopoietic Haematopoiesis (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten ...

, and

lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...

cells. In addition to its

-like effects (insulin being the main

in the body), 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 kinas ...

s: the IGF-1 receptor (IGF1R), and the insulin receptor. Its primary action is mediated by binding to its specific receptor, IGF1R, which is present on the surface of several cell types in a multitude of tissues. Binding to the IGF1R initiates intracellular signaling. IGF-1 is one of the most potent natural activators of the Akt

signaling pathway In biology, cell signaling (cell signalling in British English) is the process by which a cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all cellular life in both prokaryotes and eukary ...

, a stimulator of cell growth and proliferation, and a potent inhibitor of

programmed cell death Programmed cell death (PCD) sometimes referred to as cell, or 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 usual ...

. The IGF-1 receptor and insulin receptor are two closely related members of a

transmembrane A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...

tetrameric tyrosine kinase receptor family. They control vital brain functions, such as

survival Survival or survivorship, the act of surviving, is the propensity of something to continue existing, particularly when this is done despite conditions that might kill or destroy it. The concept can be applied to humans and other living things ...

, growth,

energy metabolism Bioenergetics is a field in biochemistry and cell biology that concerns energy flow through living systems. This is an active area of biological research that includes the study of the transformation of energy in living organisms and the study ...

longevity Longevity may refer to especially long-lived members of a population, whereas ''life expectancy'' is defined Statistics, statistically as the average number of years remaining at a given age. For example, a population's life expectancy at birth ...

, neuroprotection and neuroregeneration.

Metabolic effects

As a major

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for ...

, IGF-1 is responsible for stimulating growth of all cell types, and causing significant metabolic effects. One important metabolic effect of IGF-1 is signaling cells that sufficient

nutrients A nutrient is a substance used by an organism to survive, grow and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...

are available for them to undergo hypertrophy and

cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...

. Its effects also include inhibiting cell apoptosis and increasing 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

carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...

, 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.

The IGF system

IGF-1 is part of the insulin-like growth factor (IGF) system. This system consists of three

ligands In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ...

(

, IGF-1 and IGF-2), two tyrosine kinase receptors ( insulin receptor and IGF-1R receptor) and six ligand binding proteins (

IGFBP The insulin-like growth factor-binding protein (IGFBP) serves as a transport protein for insulin-like growth factor 1 (IGF-1). Function Approximately 98% of IGF-1 is always bound to one of six binding proteins (IGF-BP). IGFBP-3, the most abund ...

1–6). Together they play an essential role in proliferation,

, regulation of

cell growth Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

and affect almost every

organ system An organ system is a biological system consisting of a group of organ (biology), organs that work together to perform one or more bodily functions. Each organ has a specialized role in an organism body, and is made up of distinct Tissue (biolog ...

in the body. Similarly to IGF-1, IGF-2 is mainly produced in the

and after it is released into circulation, it stimulates growth and cell proliferation. IGF-2 is thought to be a

fetal A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic stage, the fetal stage of development takes place. Prenatal development is a ...

growth factor, as it is essential for a normal

embryonic development In developmental biology, animal embryonic development, also known as animal embryogenesis, is the developmental stage of an animal embryo. Embryonic development starts with the fertilization of an egg cell (ovum) by a sperm, sperm cell (spermat ...

and is highly expressed in embryonic and

neonatal In common terminology, a baby is the very young offspring of adult human beings, while infant (from the Latin word ''infans'', meaning 'baby' or 'child') is a formal or specialised synonym. The terms may also be used to refer to Juvenile (orga ...

tissues.

Variants

A splice variant of IGF-1 sharing an identical mature region, but with a different E domain is known as ''mechano-growth factor'' (MGF).

Related disorders

Laron syndrome

Acromegaly

Acromegaly Acromegaly is a disorder that results in excess growth of certain parts of the human body. It is caused by excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There ...

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 language, Greek σύνδρομον, meaning "concurrence". When a sy ...

caused by the

gland producing excess growth hormone (GH). A number of disorders may increase the pituitary's GH output, although most commonly it involves a tumor called pituitary adenoma, derived from a distinct type of cell ( somatotrophs). It leads to anatomical changes and metabolic dysfunction caused by elevated GH and IGF-1 levels. High level of IGF-1 in acromegaly is related to an increased risk of some

cancers Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

, particularly

colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...

and

thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck, ...

Use as a diagnostic test

Growth hormone deficiency

IGF-1 levels can be analyzed and used by physicians as a screening test for growth hormone deficiency (GHD),

acromegaly Acromegaly is a disorder that results in excess growth of certain parts of the human body. It is caused by excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There ...

and

gigantism Gigantism (, ''gígas'', "wiktionary:giant, giant", plural γίγαντες, ''gígantes''), also known as giantism, is a condition characterized by excessive growth and height significantly above average height, average. In humans, this conditi ...

. However, IGF-1 has been shown to be a bad diagnostic screening test for growth hormone deficiency. The ratio of IGF-1 and insulin-like growth factor-binding protein 3 has been shown to be a useful diagnostic test for GHD.

Liver fibrosis

Low serum IGF-1 levels have been suggested as a biomarker for predicting fibrosis, but not steatosis, in people with metabolic dysfunction–associated steatotic liver disease.

Causes of elevated IGF-1 levels

* Medical conditions: **

(especially when GH is also high) **

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 hormone, hormonal signs that puberty has begun. In the United States ...

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

hyperthyroidism Hyperthyroidism is a endocrine disease in which the thyroid gland produces excessive amounts of thyroid hormones. Thyrotoxicosis is a condition that occurs due to elevated levels of thyroid hormones of any cause and therefore includes hyperth ...

** some rare tumors, such as carcinoids, secreting IGF-1 * Diet: ** High-protein diet ** consumption of

dairy product Dairy products or milk products are food products made from (or containing) milk. The most common dairy animals are cow, water buffalo, goat, nanny goat, and Sheep, ewe. Dairy products include common grocery store food around the world such as y ...

s (except for cheese) ** consumption of fish * IGF-1 assay problems

Calorie restriction Calorie restriction (CR, also known as caloric restriction or energy restriction) is a dietary regimen that reduces the energy intake from foods and beverages without incurring malnutrition. The possible effect of calorie restriction on body w ...

has been found to have no effect on IGF-1 levels.

Causes of reduced IGF-1 levels

* Metabolic dysfunction–associated steatotic liver disease, especially at advanced stages of steatohepatitis and fibrosis

Health effects

Mortality

Both high and low levels of IGF‐1 increase mortality risk, with the mid‐range (120–160 ng/ml) being associated with the lowest mortality.

Dairy consumption

It has been suggested that consumption of IGF-1 in

s could increase cancer risk, particularly

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

. However, significant levels of intact IGF-1 from oral consumption are not absorbed as they are digested by gastric enzymes. IGF-1 present in food is not expected to be active within the body in the way that IGF-1 is produced by the body itself. The

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

has stated that IGF-I concentrations in milk are not significant when evaluated against concentrations of IGF-I endogenously produced in humans. A 2018 review by the Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (COC) concluded that there is "insufficient evidence to draw any firm conclusions as to whether exposure to dietary IGF-1 is associated with an increased incidence of cancer in consumers". Certain dairy processes such as

fermentation Fermentation is a type of anaerobic metabolism which harnesses the redox potential of the reactants to make adenosine triphosphate (ATP) and organic end products. Organic molecules, such as glucose or other sugars, are catabolized and reduce ...

are known to significantly decrease IGF-1 concentrations. The

British Dietetic Association The British Dietetic Association (BDA) is a trade union for dietitians in the United Kingdom. It was founded in 1936 and became a certified union in 1982. It is affiliated to the Trades Union Congress and the Scottish Trades Union Congress. H ...

has described the idea that milk promotes hormone related cancerous tumor growth as a myth, stating "no link between dairy containing diets and risk of cancer or promoting cancer growth as a result of hormones".

Cardiovascular disease

Increased IGF-1 levels are associated with a 16% lower risk of

and a 28% reduction of cardiovascular events.

Diabetes

Low IGF-1 levels are shown to increase the risk of developing

type 2 diabetes Type 2 diabetes (T2D), 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 ...

and insulin resistance. On the other hand, a high IGF-1

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

in people with diabetes may delay or prevent diabetes-associated complications, as it improves impaired small

blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...

function. IGF-1 has been characterized as an insulin sensitizer. Low serum IGF‐1 levels can be considered an indicator of liver fibrosis in type 2 diabetes mellitus patients.

References

External links

* * {{DEFAULTSORT:Insulin-Like Growth Factor 1 Peptide hormones Hormones of the somatotropic axis Insulin-like growth factor receptor agonists Insulin receptor agonists Aging-related proteins Neurotrophic factors Developmental neuroscience de:IGF-1