Interchangeability of Insulin and IGF-1

Molecular Structure

What is IGF-1?

IGF-1 is a hormone with anabolic effects in adults that plays an important role in childhood growth and is similar in molecular structure to insulin. According to the Wikipedia article on IGF-1, it consists of 70 amino acids in a single chain with three disulfide bridges. IGF-1 is encoded by the IGF1 gene.

What role does the IGF-1 receptor play in growth hormone activity?

The human IGF-1 receptor is a product of a single gene spanning over 100 kb of genomic DNA located on the long arm of chromosome 15q25–26, which contains 21 exons. Cited from the study conducted by the British Medical Journal in 2000, this receptor plays a key role in the growth hormone activity. It is associated with numerous physiological processes such as metabolism, cell proliferation, and cell death.

What is the molecular mechanism of one amino acid sequence encoding two three-dimensional structures?

The crystal structure of mini-IGF-1 (2), an artificial analog of IGF-1, was solved by the SAD/SIRAS method at RCSB PDB in 2004, revealing the molecular mechanism of one amino acid sequence encoding two three-dimensional structures. This phenomenon has been mystifying scientists for a long time.

Biological Function

What are the similarities and differences between insulin and IGF-I?

Insulin and IGF-I are both pleiotropic hormones that regulate vital metabolic and developmental processes, although insulin has primarily been linked with metabolic activities. As indicated by a study published in the journal Genomics in 2008 by researchers at the University of California, San Diego, insulin and IGF-I have similarities and differences in terms of structure, signaling pathways, and post-translational modifications.

What is the role of the type 1 insulin-like growth factor receptor?

The type 1 insulin-like growth factor receptor (IGF-1R) is a transmembrane tyrosine kinase that is widely expressed in fetal and postnatal tissues and is activated upon binding of the secreted growth factor ligands IGF-1 and IGF-2, eliciting a range of cellular responses such as proliferation. Via a study published by the National Center for Biotechnology Information (NCBI) in 2000, the structure and function of this receptor are essential for normal growth and development.

What role does IGF1 play in tissue growth?

Insulin-Like Growth Factor 1 (IGF1) is a 70-amino acid polypeptide hormone that mediates prenatal and postnatal growth, primarily produced in the liver. According to a study by ScienceDirect in 2020, IGF1 serves as an endocrine, paracrine and autocrine hormone that mediates the action of GH in peripheral tissues such as muscle.

Chemical Composition

What is IGF1?

Insulin-Like Growth Factor 1 (IGF1) is a 70-amino acid polypeptide hormone that mediates prenatal and postnatal growth, mainly produced in the liver. Via ScienceDirect Topics, IGF1 serves as an endocrine, paracrine and autocrine hormone, mediating the action of GH in peripheral tissues such as muscle.

What role does the IGF-1 receptor play?

The IGF-1 receptor is a single copy gene located on the long arm of chromosome 15q25–26, which plays an important role in growth hormone production. As reported by a study conducted by the British Medical Journal in 2000, the gene contains 21 exons and spans over 100 kb of genomic DNA. It has been found to be involved in other physiological processes such as the metabolism of proteins and carbohydrates.

Can maternal diabetes affect the placenta?

The study concluded that maternal diabetes can impair the content and phosphorylation of insulin and IGF-1 receptors in the placenta, as reported by the University of São Paulo in 2021. This could lead to structural and functional alterations in the placenta of diabetic women.

Receptor Sites

What role does IGF-I play in the development of insulin resistance?

The study concluded that low and high IGF-I levels are associated with impaired glucose tolerance and a higher risk of type 2 diabetes, as reported by researchers from the journal Care in 2012. This suggests that IGF-I plays an important role in the development of insulin resistance and its related conditions. Research has found that IGF-I stimulates muscle cell glucose uptake and utilization, which can further contribute to insulin resistance.

What are the similarities and differences between insulin and IGF-I and IGF-II?

Insulin and the insulin-like growth factors (IGF-I and IGF-II) are hormones that play important roles in regulating metabolism and development, though insulin has primarily been studied for its metabolic effects. As stated by a study conducted by the National Center for Biotechnology Information in 2008, IGF-I and IGF-II have been found to have many similarities, such as their ability to bind to common receptors and activate similar signaling cascades, as well as differences, such as their different affinities for these receptors.

How does insulin binding to its receptor affect NO production?

Insulin binding to its receptor increases NO production in the endothelium, as demonstrated by several studies from various laboratories (). Sourced from a study from Elegant laboratories published in Diabetes, 2012, this effect is due to the activation of the insulin receptor substrate (IRS)-1 and phosphatidylinositol 3-kinase (PI3K) pathways. IGF-1 receptors have also been shown to regulate NO production.

Metabolism

Does IGF-1 deficiency have any association with metabolic syndrome?

IGF-1 deficiency is associated with metabolic syndrome, which is characterized by impaired lipid profile, insulin resistance, increased glucose levels, obesity, and cardiovascular disease. Mentioned in a study published in Translational Medicine in 2016, IGF-1 deficiency has been consistently linked to metabolic syndrome. Studies have shown that the low circulatory levels of IGF-1 may lead to an increased risk of developing metabolic syndrome.

What role do insulin and IGF 1 play in learning and memory?

Insulin and IGF 1 play a significant role in learning and memory, as well as anxiety-like behavior, according to research in mice from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2019. This research has uncovered a link between insulin action, metabolism, and cognitive function.

What is the role of IGF-1 in CNS development?

Insulin-Like Growth Factor 1 (IGF-1) is a hormone with vital roles in CNS development and cellular neuroplasticity, as demonstrated by a study published in 2016 by the National Center for Biotechnology Information. IGF-1 is also known to be a phylogenetically ancient neurotrophic hormone. Studies have shown that IGF-1 has potent effects on brain plasticity, allowing the CNS to adapt to changes.

Transport

What role do IGFBPs play in IGF I and II transport?

The Insulin like Growth Factor Binding Proteins (IGFBPs) regulate the transport of Insulin-like Growth Factors I and II (IGF I and IGF II). This is evidenced by the conserved N terminal and C terminal regions responsible for binding IGF I and II, which share 50% amino acid identity. Via Reactome's research published on their website in 2020, this regulation of IGF transport plays an important role in maintaining homeostasis.

What role do insulin and IGF-1 have in the clearance of amyloid-beta from the brain?

Insulin and IGF-1 have potential roles in helping to clear amyloid-beta (A?) from the brain, as they increase secretion of A? and elevate the fraction of A? in the brain, according to a study published in Neurobiology of Aging in 2003 by researchers at the University of Toronto. IGF-1 has been linked to increased transport of A?-carrier proteins into the brain.

What is IGF1?

Insulin-Like Growth Factor 1 (IGF1) is a 70-amino acid polypeptide hormone primarily produced in the liver that mediates prenatal and postnatal growth. As an endocrine, paracrine, and autocrine hormone, it is a major mediator of the action of GH in peripheral tissues such as muscle, as reported by ScienceDirect in 2020. IGF1 is also associated with the regulation of cell growth and metabolism.

Interaction with Other Proteins

What are the interactions between insulin and IGF-I/II?

This review concludes that there are complex interactions between insulin and IGF-I/II, resulting in an expanded range of activities and a greater understanding of the signalling pathways mediated by both receptors. As reported on pubmed.ncbi.nlm.nih.gov in 2008, research into the insulin and IGF signalling pathways has been intensive in recent years. IGF-I/II signalling pathways have been found to play a role in a variety of cellular processes, including metabolism, growth, and development.

What role do IGF-Binding Proteins play in IGF signaling?

IGF-Binding Proteins regulate IGF signaling globally and locally by binding to IGF with an equal or greater affinity than the IGF1 receptor, increasing its half-life in the circulation and blocking its potential binding to the insulin receptor, as reported by researchers from the National Center for Biotechnology Information in 2018. In addition, IGFBPs have been linked to a range of physiological and pathological processes.

What regulates IGFBP-3?

IGF-1 is primarily carried in the body by a ternary complex consisting of one molecule of IGF-1, one molecule of IGFBP-3, and one molecule of an 88 kDa protein called acid labile subunit. Cited on the study conducted by National Center for Biotechnology Information (NCBI) in 2008, IGFBP-1 is regulated by insulin and IGF-1, and IGFBP-3 is regulated mainly by GH but also to some extent by IGF-1 and insulin.

Biological Activity

Can IGF-I levels predict type 2 diabetes risk?

The study found that low and high IGF-I levels are related to impaired glucose tolerance and a higher risk of type 2 diabetes, according to the research conducted by Mar 13, 2012 by the Department of Endocrinology and Metabolism, China Medical University Hospital in Taiwan. This suggests that IGF-I levels may be an important indicator to assess the risk of type 2 diabetes. Research has shown that people with type 2 diabetes have lower IGF-I levels than those without.

What is the role of insulin in pancreas agenesis patients?

Insulin has the same origin and similar structure to IGF-1, and acts as a growth hormone with protein anabolic activity, according to a study conducted by the National Center of Biotechnology Information (NCBI) in 2004. It also stimulates IGF-1 synthesis in pancreas agenesis patients, leading to shorter babies and obese children with insulin resistance.

What role does IGF1 play in regulating cell activity?

Insulin-Like Growth Factor 1 (IGF1) is a 70-amino acid polypeptide hormone primarily produced in the liver that serves as a major mediator of prenatal and postnatal growth, as well as an endocrine, paracrine, and autocrine hormone mediator of GH in peripheral tissues. As reported by a study published by the National Institutes of Health in 2020, IGF1 plays a major role in regulating cell proliferation and differentiation.

Biological Half-Life

What is the relationship between IGF-I levels and insulin resistance?

The current study concluded that there is an association between IGF-I levels and insulin resistance, as reported by the Universidad Nacional Autonoma de Mexico on diabetesjournals.org in 2012. This relationship was further confirmed with data showing that low and high IGF-I levels are related to impaired glucose tolerance and a higher risk of type 2 diabetes.

How does maternal diabetes affect insulin and IGF-1 receptors in the placenta?

The study concluded that maternal diabetes impairs the expression and phosphorylation of insulin and IGF-1 receptors in the placenta. This was reported by researchers from the University of Granada, Spain on PubMed in 2021. It is known that these alterations may affect placental function and fetal growth.

Can IGF-1 deficiency lead to metabolic syndrome?

IGF-1 deficiency is linked to metabolic syndrome, a clinical manifestation consisting of impaired lipid profile, insulin resistance, increased glucose levels, obesity, and cardiovascular disease. This is evidenced by consistent research conducted by Jan 6, 2016 in Translational Medicine from BioMed Central. IGF-1 replacement therapy could be a potential approach to tackle the metabolic syndrome.

Therapeutic Uses

What role does the IGF axis play in growth and disease?

The IGF axis plays an important role in both normal growth and development, and in the pathogenesis of cancer and endocrine disorders. This review article discussed the functions of ligand-induced IGF axis activation and the evidence for its involvement in disease, as published by the National Center for Biotechnology Information in 2019. In addition, the article highlighted how therapeutic targeting of the IGF axis may be beneficial in treating these diseases.

Can insulin and IGF-1 be potential treatments for Alzheimer's disease?

Insulin and IGF-1 could be potential treatments for Alzheimer's disease, as they are both present in rodent and human brain. As stated by the study published in Neuroscience and Biobehavioral Reviews in 2003 by researchers from the University of California, an appropriate route of administration should be used for insulin. IGF-1 can be administered systemically and safely.

What indication was the first IGF-1R antibody drug initially pursued for?

The first antibody drug targeting the insulin-like growth factor 1 receptor (IGF-1R) was approved by regulatory authorities in January 2020, allowing its use for the treatment of cancer. As indicated by a study published by Nature in April 2020, this drug was initially pursued for a different indication. This drug has shown promise in treating Graves’ disease.

Source:

• Wikipedia : Insulin-like growth factor, - Wikipedia.
• Nih : insulin, IGF, -I.
• Sciencedirect : Insulin-Like Growth Factor, an overview, ScienceDirect Topics.
• Diabetesjournals : The Association, IGF-I, Insulin Resistance.
• Biomedcentral : Insulin-like growth factor-1 deficiency, metabolic syndrome.