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Insulin like growth factor-1

Synthesized by liver cells.

Insulin-like growth factor 1

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

A hormone similar in molecular structure to insulin.

Has an important role in childhood growth and continues to have anabolic effects in adults.

A polypeptide that has mitogenic and anti-apoptotic effects.

Insulin like growth factor 1 (IGF-1) is positively associated with the risk of several cancers by stimulating proliferation and inhibiting apoptosis.
Individuals who consume a vegan diet and significantly lower levels of IGF1 and higher levels of IGF binding proteins one and two which may be associated with the specific effects of plant proteins and lower overall protein intake compared with a western diet.

A protein that in humans is encoded by the IGF1 gene, on chromosome 12

Band 12q23.2

The liver is the principal site of IGF-1 production.

IGF-1 has growth-stimulating effects on a wide variety of tissues.

IGF-1 is bound to IGF binding proteins at approximately 99%.

IGF-1 is also generated within target tissues.

It is both an endocrine and an autocrine/paracrine hormone.

It has stimulatory effects on osteoblast and chondrocyte activity to promote bone growth.

Its molecular functions include :

hormone activity

insulin receptor binding

growth factor activity

Integrin binding

protein binding

insulin-like growth factor receptor binding

Biological process of positively regulatng the transcription region of DNA binding.

skeletal system development

positive regulation of glucose import

movement of cell or subcellular component

muscle organ development

positive regulation of Ras protein signal transduction

response to heat

positive regulation of cardiac muscle hypertrophy

positive regulation of smooth muscle cell migration

DNA replication

positive regulation of insulin-like growth factor receptor signaling pathway

phosphatidylinositol 3-kinase signaling

positive regulation of DNA binding

Ras protein signal transduction

cell proliferation

positive regulation of mitotic nuclear division

positive regulation of trophectodermal cell proliferation

positive regulation of glycogen biosynthetic process

positive regulation of protein import into nucleus, translocation

positive regulation of fibroblast proliferation

ERK1 and ERK2 cascade

negative regulation of extrinsic apoptotic signaling pathway

cell activation

negative regulation of oocyte development

positive regulation of transcription, DNA-templated

bone mineralization

regulation of peptidyl-tyrosine phosphorylation

regulation of MAPK cascade

proteoglycan biosynthetic process

regulation of activated T cell proliferation

regulation of epithelial cell proliferation

negative regulation of release of cytochrome c from mitochondria

protein stabilization

myotube cell development

positive regulation of DNA replication

myoblast proliferation

skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration

positive regulation of protein secretion

positive regulation of glycoprotein biosynthetic process

regulation of gene expression

phosphatidylinositol-mediated signaling

positive regulation of smooth muscle cell proliferation

cellular protein metabolic process

muscle hypertrophy

protein kinase B signaling

positive regulation of cell migration

platelet degranulation

positive regulation of phosphatidylinositol 3-kinase signaling

myoblast differentiation

glycolate metabolic process

positive regulation of glycolytic process

negative regulation of smooth muscle cell apoptotic process

signal transduction

positive regulation of transcription from RNA polymerase II promoter

positive regulation of cell growth involved in cardiac muscle cell development

activation of MAPK activity

positive regulation of cell proliferation

positive regulation of osteoblast differentiation

activation of protein kinase B activity

insulin-like growth factor receptor signaling pathway

negative regulation of apoptotic process

positive regulation of tyrosine phosphorylation of STAT protein

It is produced primarily by the liver as an endocrine hormone as well as in target tissues in a paracrine/autocrine fashion.

Production is stimulated by growth hormone (GH) and can be slowed by undernutrition, growth hormone insensitivity, lack of growth hormone receptors, or failures of the downstream signaling pathway.

Approximately 98% of IGF-1 is always bound to one of 6 binding proteins.

It is produced throughout life.

Its highest rate of production occurs during the pubertal growth spurt. with its lowest levels occur in infancy and old age.

Levels vary by: insulin levels, time of day, age, gender, exercise stress level, nutritional status, BMI, comorbid illnesses, ethnicity, and hormonal status.

It is a primary mediator of the effects of growth hormone.

Growth hormone is produced in the anterior pituitary gland, is released into the blood stream, and then stimulates the liver 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, cartilage, bone, liver, kidney, nerves, skin, hematopoietic cell, and lungs.

Has insulin-like effects, and can also regulate cell growth and development, especially in nerve cells, as well as cellular DNA synthesis.

Its major action is mediated by binding to its specific receptor, the insulin-like growth factor 1 receptor (IGF1R).

The insulin-like growth factor 1 receptor is present on many cell types in many tissues.

When binding to the IGF1R, a receptor tyrosine kinase, initiates intracellular signaling; IGF-.

IGF-1 is one of the most potent natural activators of the AKT signaling pathway, a stimulator of cell growth and proliferation, and a potent inhibitor of programmed cell death.

IGF-1 binds to at least two cell surface receptors: the IGF-1 receptor (IGF1R), and the insulin receptor.

The IGF-1 receptor binds IGF-1 at significantly higher affinity than the IGF-1 that is bound to the insulin receptor.

The IGF-1 receptor is a receptor tyrosine kinase – meaning it signals by causing the addition of a phosphate molecule on particular tyrosines.

IGF-1 activates the insulin receptor at approximately 0.1 times the potency of insulin.

Insulin-like growth factor 1 receptor and other tyrosine kinase growth factor receptors signal through multiple pathways: phosphatidylinositol-3 kinase (PI3K) and its downstream partner, the mammalian target of rapamycin (mTOR).

Diseases characterized by inability to make or respond to IGF-1 produce a distinctive type of dwarfism, Laron syndrome.

With Laron syndrome patients do not respond to growth hormone treatment due to a lack of GH receptors.

Patients with Laron syndrome have strikingly low rates of cancer and diabetes.

 

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