Insulin-like growth factor - AbsoluteAstronomy.com

The insulin-like growth factors (IGFs) are protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s with high sequence similarity

Homology (biology)

Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...

to insulin

Insulin

Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

. IGFs are part of a complex system

Complex system

A complex system is a system composed of interconnected parts that as a whole exhibit one or more properties not obvious from the properties of the individual parts....

that cells use to communicate with their physiologic

Physiology

Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...

environment. This complex system (often referred to as the IGF "axis") consists of two cell-surface receptors (IGF1R and IGF2R), two ligand

Ligand

In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...

s (IGF-1 and IGF-2), a family of six high-affinity IGF-binding proteins (IGFBP 1-6), as well as associated IGFBP degrading enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s, referred to collectively as protease

Protease

A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

IGF1/GH Axis

The IGF "axis" is also commonly referred to as the Growth Hormone/IGF1 Axis. Insulin-like growth factor 1

Insulin-like growth factor 1

Insulin-like growth factor 1 also known as somatomedin C is a protein that in humans is encoded by the IGF1 gene. IGF-1 has also been referred to as a "sulfation factor" and its effects were termed "nonsuppressible insulin-like activity" in the 1970s.IGF-1 is a hormone similar in molecular...

(IGF-1) is mainly secreted by the liver as a result of stimulation by growth hormone

Growth hormone

Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...

(GH). IGF-1 is important for both the regulation of normal physiology, as well as a number of pathological states, including cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. The IGF axis has been shown to play roles in the promotion of cell proliferation and the inhibition of cell death (apoptosis

Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

). Insulin-like growth factor 2

Insulin-like growth factor 2

Insulin-like growth factor 2 is one of three protein hormones that share structural similarity to insulin.-Gene structure:In humans, the IGF2 gene is located on chromosome 11p15.5, a region which contains numerous imprinted genes. In mice this homologous region is found at distal chromosome 7...

(IGF-2) is thought to be a primary growth factor

Growth factor

A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....

required for early development while IGF-1 expression is required for achieving maximal growth. Gene knockout

Gene knockout

A gene knockout is a genetic technique in which one of an organism's genes is made inoperative . Also known as knockout organisms or simply knockouts, they are used in learning about a gene that has been sequenced, but which has an unknown or incompletely known function...

studies in mice have confirmed this, though other animals are likely to regulate the expression of these genes in distinct ways. While IGF-2 may be primarily fetal

Fetus

A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...

in action it is also essential for development and function of organs such as the brain

Brain

The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

, liver

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

and kidney

Kidney

The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

.

Factors that are known to cause variation in the levels of GH and IGF-1 in the circulation include an individuals genetic make-up, the time of day, their age, sex, exercise status, stress levels, genetics, nutrition level and body mass index

Body mass index

The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...

(BMI), disease state, race, estrogen status and xenobiotic

Xenobiotic

A xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it. It can also cover substances which are present in much higher concentrations than are usual...

intake.

IGF-I has an involvement in regulating neural development

Neural development

Neural development comprises the processes that generate, shape, and reshape the nervous system, from the earliest stages of embryogenesis to the final years of life. The study of neural development aims to describe the cellular basis of brain development and to address the underlying mechanisms...

including neurogenesis

Neurogenesis

Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...

, myelination, synaptogenesis

Synaptogenesis

Synaptogenesis is the formation of synapses. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development...

, and dendritic branching and neuroprotection

Neuroprotection

Neuroprotection within the nervous system protects neurons from apoptosis or degeneration, for example following a brain injury or as a result of chronic neurodegenerative diseases....

after neuronal damage. Increased serum levels of IGF-I in children link to higher IQ.

IGF-1 shape the development of the cochlea

Cochlea

The cochlea is the auditory portion of the inner ear. It is a spiral-shaped cavity in the bony labyrinth, making 2.5 turns around its axis, the modiolus....

through controlling apoptosis

Apoptosis

. Its deficit can cause hearing

Hearing (sense)

Hearing is the ability to perceive sound by detecting vibrations through an organ such as the ear. It is one of the traditional five senses...

loss. Serum level of it also underlies a correlation between short height

Human height

Human height is the distance from the bottom of the feet to the top of the head in a human body standing erect.When populations share genetic background and environmental factors, average height is frequently characteristic within the group...

and reduced hearing abilities particularly around 3–5 years of age, and at age 18 (late puberty

Puberty

Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...

IGF Receptors

The IGF's are known to bind the IGF-1 receptor

IGF-1 Receptor

The Insulin-like Growth Factor 1 Receptor is a transmembrane receptor that is activated by IGF-1 and by the related growth factor IGF-2. It belongs to the large class of tyrosine kinase receptors. This receptor mediates the effects of IGF-1, which is a polypeptide protein hormone similar in...

, the insulin receptor

Insulin receptor

In molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. It belongs to the large class of tyrosine kinase receptors....

, the IGF-2 receptor

Insulin-like growth factor 2 receptor

In the fields of biochemistry and cell biology, the insulin-like growth factor 2 receptor , also called the cation-independent mannose-6-phosphate receptor is a protein that in humans is encoded by the IGF2R gene...

, the insulin-related receptor and possibly other receptors. The IGF-1 receptor

IGF-1 Receptor

is the "physiologic" receptor - IGF-1 binds to it at significantly higher affinity than it binds the insulin receptor. Like the insulin receptor, the IGF-1 receptor is a receptor tyrosine kinase

Receptor tyrosine kinase

Receptor tyrosine kinases s 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 kinase proteins....

- meaning the receptor signals by causing the addition of a phosphate molecule on particular tyrosines. The IGF-2 receptor only binds IGF-2 and acts as a "clearance receptor" - it activates no intracellular signalling pathways, functioning only as an IGF-2 sequestering agent and preventing IGF-2 signalling.

Organs and tissues affected by IGF-1

Since many distinct tissue types express the IGF-1 receptor

IGF-1 Receptor

, IGF-1's effects are diverse. It acts as a neurotrophic factor, inducing the survival of neurons. It causes skeletal muscle

Skeletal muscle

Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...

hypertrophy

Hypertrophy

Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It should be distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number...

, by inducing protein synthesis, and by blocking muscle atrophy

Muscle atrophy

Muscle atrophy, or disuse atrophy, is defined as a decrease in the mass of the muscle; it can be a partial or complete wasting away of muscle. When a muscle atrophies, this leads to muscle weakness, since the ability to exert force is related to mass...

. It is protective for cartilage

Cartilage

Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...

cells, and is associated with activation of osteocytes, and thus may be an anabolic factor for bone

Bone

Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...

. Since at high concentrations it is capable of activating the insulin receptor

Insulin receptor

In molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. It belongs to the large class of tyrosine kinase receptors....

, it can also complement for the effects of insulin

Insulin

IGF-Binding Proteins

IGF-1 and IGF-2 are regulated by a family of proteins known as the IGF-Binding Proteins. These proteins help to modulate IGF action in complex ways that involve both inhibiting IGF action by preventing binding to the IGF-1 receptor as well as promoting IGF action possibly through aiding in delivery to the receptor and increasing IGF half-life. Currently, there are 6 characterized IGF Binding Proteins (IGFBP1-6). There is currently significant data suggesting that IGFBPs play important roles in addition to their ability to regulate IGFs.

Diseases affected by IGF

Studies of recent interest show that the Insulin/IGF axis play an important role in aging

Senescence

Senescence or biological aging is the change in the biology of an organism as it ages after its maturity. Such changes range from those affecting its cells and their function to those affecting the whole organism...

. Nematode

Nematode

The nematodes or roundworms are the most diverse phylum of pseudocoelomates, and one of the most diverse of all animals. Nematode species are very difficult to distinguish; over 28,000 have been described, of which over 16,000 are parasitic. It has been estimated that the total number of nematode...

s, fruit-flies

Drosophila melanogaster

Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...

and other organisms have an increased life span when the gene equivalent to the mammalian insulin is knocked out

Gene knockout

. It is somewhat difficult to relate this finding to the mammal, however, because in the smaller organism there are many genes (at least 37 in the nematode) that are "insulin-like" or "IGF-1-like", whereas in the mammals insulin-like proteins comprise only 7 members (insulin

Insulin

, IGF

IGF

IGF may stand for:* Insulin-like growth factor* Independent Games Festival* Internet Governance Forum* Identity Governance Framework* Inoki Genome Federation* International Golf Federation* International Gymnastics Federation* International Go Federation...

s, relaxin

Relaxin

Relaxin is a protein hormone first described in 1926 by Frederick Hisaw.The relaxin-like peptide family belongs in the insulin superfamily and consists of 7 peptides of high structural but low sequence similarity; relaxin-1 , 2 and 3 , and the insulin-like peptides, INSL3, INSL4, INSL5 and INSL6...

s, EPIL, and relaxin-like factor) and have apparently distinct roles with some but less crosstalk. On the other hand, simpler organisms typically have fewer receptors (only 1 known in the nematode) and the roles of these other insulins are unknown. Furthermore these animals do not have specialized organs (Islets of Langerhans

Islets of Langerhans

The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas...

), which sense insulin in response to glucose homeostasis. Therefore it is an open question as to whether either IGF1 or insulin in the mammal may perturb aging, although there is strong suggestion dietary restriction phenomena are related.

Other studies are beginning to uncover the important role the IGFs play in diseases such as cancer

Cancer

and diabetes, showing for instance that IGF-1 stimulates growth of both prostate and breast cancer cells. Researchers are not in complete agreement about the degree of cancer risk that IGF-1 poses.

IGF1/GH Axis

IGF Receptors

Organs and tissues affected by IGF-1

IGF-Binding Proteins

Diseases affected by IGF

See also