Insulin-like growth factor 2
Encyclopedia
Insulin-like growth factor 2 (IGF-2) is one of three protein hormone
s that share structural similarity to insulin
.
is located on chromosome
11p15.5, a region which contains numerous imprinted genes. In mice this homologous region is found at distal chromosome 7. In both organisms, Igf2 is imprinted, with expression resulting favourably from the paternally inherited allele
.
The protein CTCF
is involved in repressing expression
of the gene, by binding to the H19
imprinting control region (ICR) along with Differentially-methylated Region-1 (DMR1) and Matrix Attachment Region -3 (MAR3). These three DNA sequence
s bind to CTCF
in a way that limits downstream enhancer access to the Igf2 region. The mechanism in which CTCF binds to these regions is currently unknown, but could include either a direct DNA-CTCF interaction or it could possibly be mediated by other proteins
(also called the cation-independent mannose 6-phosphate receptor
), which acts as a signalling antagonist; that is, to prevent IGF2 responses.
.
In the process of Folliculogenesis, IGF2 is created by Theca cells to act in an autocrine manner on the theca cells themselves, and in a paracrine manner on Granulosa cells in the ovary. IGF2 promotes granulosa cell proliferation during the follicular phase of the menstrual cycle, acting alongside Follicle Stimulating Hormone (FSH). After ovulation has occurred, IGF-2 promotes progesterone
secretion during the luteal phase of the menstrual cycle together with Luteinizing Hormone (LH). Thus, IGF2 acts as a Co-hormone together with both FSH and LH.
A study at the Mount Sinai School of Medicine found that IGF-II may be linked to memory. The study found that it may play a key role in memory and could potentially be used to treat Alzheimer's Disease
.. A study at the European Neuroscience Institute-Goettingen (Germany) found that fear extinction-induced IGF2/IGFBP7
signalling promotes the survival of 17–19-day-old newborn hippocampal neurons. This suggests that therapeutic strategies that enhance IGF2 signalling and adult neurogenesis
might be suitable to treat diseases linked to excessive fear memory such as PTSD.
cell tumours, causing hypoglycemia
. Doege-Potter syndrome
is a paraneoplastic syndrome
in which hypoglycemia is associated with the presence of one or more non-islet fibrous tumor
s in the pleural cavity
.
Loss of imprinting of IGF2 is a common feature in tumours seen in Beckwith-Wiedeman syndrome.
with IGFBP3
and Transferrin
.
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s that share structural similarity 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....
.
Gene structure
In humans, the IGF2 geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
is located on chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
11p15.5, a region which contains numerous imprinted genes. In mice this homologous region is found at distal chromosome 7. In both organisms, Igf2 is imprinted, with expression resulting favourably from the paternally inherited allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
.
The protein CTCF
CTCF
Transcriptional repressor CTCF also known as 11-zinc finger protein or CCCTC-binding factor is a transcription factor that in humans is encoded by the CTCF gene...
is involved in repressing expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of the gene, by binding to the H19
H19 (gene)
H19 is a gene for a long noncoding RNA, found in humans and elsewhere. This gene seems to have a role in some forms of cancer.The H19 gene is also known as ASM, ASM1 and BWS, among others....
imprinting control region (ICR) along with Differentially-methylated Region-1 (DMR1) and Matrix Attachment Region -3 (MAR3). These three DNA sequence
DNA sequence
The sequence or primary structure of a nucleic acid is the composition of atoms that make up the nucleic acid and the chemical bonds that bond those atoms. Because nucleic acids, such as DNA and RNA, are unbranched polymers, this specification is equivalent to specifying the sequence of...
s bind to CTCF
CTCF
Transcriptional repressor CTCF also known as 11-zinc finger protein or CCCTC-binding factor is a transcription factor that in humans is encoded by the CTCF gene...
in a way that limits downstream enhancer access to the Igf2 region. The mechanism in which CTCF binds to these regions is currently unknown, but could include either a direct DNA-CTCF interaction or it could possibly be mediated by other proteins
Protein structure
IGF-2 exerts its effects by binding to the IGF-1 receptor. IGF2 may also bind to the IGF-2 receptorInsulin-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...
(also called the cation-independent mannose 6-phosphate receptor
Mannose 6-phosphate receptor
In the fields of biochemistry and cell biology, mannose 6-phosphate receptors are proteins that bind newly synthesized lysosomal hydrolases in the trans-Golgi network and deliver them to pre-lysosomal compartments. There are two different MPRs, one of ~300kDa and a smaller, dimeric receptor of...
), which acts as a signalling antagonist; that is, to prevent IGF2 responses.
Function
The major role of IGF2 is as a growth promoting hormone during gestationGestation
Gestation is the carrying of an embryo or fetus inside a female viviparous animal. Mammals during pregnancy can have one or more gestations at the same time ....
.
In the process of Folliculogenesis, IGF2 is created by Theca cells to act in an autocrine manner on the theca cells themselves, and in a paracrine manner on Granulosa cells in the ovary. IGF2 promotes granulosa cell proliferation during the follicular phase of the menstrual cycle, acting alongside Follicle Stimulating Hormone (FSH). After ovulation has occurred, IGF-2 promotes progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
secretion during the luteal phase of the menstrual cycle together with Luteinizing Hormone (LH). Thus, IGF2 acts as a Co-hormone together with both FSH and LH.
A study at the Mount Sinai School of Medicine found that IGF-II may be linked to memory. The study found that it may play a key role in memory and could potentially be used to treat Alzheimer's Disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.. A study at the European Neuroscience Institute-Goettingen (Germany) found that fear extinction-induced IGF2/IGFBP7
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 in tissue as well as in modulating IGF binding to its receptors. IGFBP7 binds to IGF with high...
signalling promotes the survival of 17–19-day-old newborn hippocampal neurons. This suggests that therapeutic strategies that enhance IGF2 signalling and adult 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...
might be suitable to treat diseases linked to excessive fear memory such as PTSD.
Diseases
It is sometimes produced in excess in isletIslets 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...
cell tumours, causing hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
. Doege-Potter syndrome
Doege-Potter syndrome
Doege-Potter syndrome is a paraneoplastic syndrome in which hypoglycemia is associated with the presence of one or more non-islet fibrous tumors in the pleural cavity. The hypoglycemia is the result of the tumors producing insulin-like growth factor 2...
is a paraneoplastic syndrome
Paraneoplastic syndrome
A paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors excreted by tumor cells or by an immune response against the tumor...
in which hypoglycemia is associated with the presence of one or more non-islet fibrous tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s in the pleural cavity
Pleural cavity
In human anatomy, the pleural cavity is the potential space between the two pleura of the lungs. The pleura is a serous membrane which folds back onto itself to form a two-layered, membrane structure. The thin space between the two pleural layers is known as the pleural cavity; it normally...
.
Loss of imprinting of IGF2 is a common feature in tumours seen in Beckwith-Wiedeman syndrome.
Interactions
Insulin-like growth factor 2 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with IGFBP3
IGFBP3
Insulin-like growth factor-binding protein 3, also known as IGFBP3, is a protein that, in humans, is encoded by the IGFBP3 gene.- Function :...
and Transferrin
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...
.