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= Insulin-like growth factor 1 =
<Structure load='1gzr' size='400' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />


<StructureSection load='1gzr' size='340' side='right' caption='Structural basis for IGF1 protein with N-DODECYL-N,N-DIMETHYL-3-AMMONIO-1-PROPANESULFONATE ligand' scene=''>
'''Insulin-like Growth Factor''' (IGF1) is a member of the insulin protein family. '''Insulin''' is an essential endocrine protein. Indeed, it is the only hypoglycemic hormone of the human body. This protein is secreted in the beta cells of the Langerhans’ islet in the pancreas and takes part in the glycogenesis. This molecule helps the transportation of glucose into the cells, thus reducing the blood sugar rate, contrary to glucagon.
 
'''Insulin''' is a very important endocrine protein. Indeed, it is the only hypoglycemic hormone of the human body. This protein is secreted in the beta cells of the Langerhans’ islet in the pancreas and takes part in the glycogenesis. This molecule helps the transportation of glucose into the cells, thus reducing the blood sugar rate, contrary to glucagon.
Insulin also has a huge effect on growth and thereby has a lot of structural similarities with its main associated growth factor: '''IGF1''', aka somatomedin. Both share lots of properties thanks to their 60% similarity.
Insulin also has a huge effect on growth and thereby has a lot of structural similarities with its main associated growth factor: '''IGF1''', aka somatomedin. Both share lots of properties thanks to their 60% similarity.
IGF1 is a peptidic hormone of 69 amino acids which is secreted by the liver.
IGF1 is a peptidic hormone of 69 amino acids which is secreted by the liver.
This protein deals with a large scale of regulations, from growth to nutrition and it is even implied in stress response, breeding and longevity.<ref>Patrick Jouandin. Rôle de la voie de signalisation Insuline dans le couplage des informations nutritionnelles et développementales au cours de l'ovogenèse chez la drosophile.  Sciences agricoles.Université Nice Sophia Antipolis, 2013.  Français.<NNT : 2013NICE4102>.<tel-00932409></ref>.
This protein deals with a large scale of regulations, from growth to nutrition and it is even implied in stress response, breeding and longevity.<ref>Patrick Jouandin. Rôle de la voie de signalisation Insuline dans le couplage des informations nutritionnelles et développementales au cours de l'ovogenèse chez la drosophile.  Sciences agricoles.Université Nice Sophia Antipolis, 2013.  Français.<NNT : 2013NICE4102>.<tel-00932409></ref>.
It is the main actor in primary growth cell control.
It is the main actor in primary growth cell control.


== History ==
== History ==
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[[Image:IGF1.png|900 px]]
[[Image:IGF1.png|900 px]]


Its 3D structure is shown on the right.
 
<Structure load='4xss' size='250' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
 
 
 




=== Stimulating interaction : IGF1 - IGF1R ===
=== Stimulating interaction : IGF1 - IGF1R ===
'''IGF1R''' is a transmembrane protein receptor. It is composed of two alpha subunits and two tyrosine beta subunits. Both alpha subunits are cysteine-rich region and therefore linked with a disulfide bond. Ligand-binding on alpha subunit induces activation of beta subunit by autophosphorylation. It further leads to activation of the Akt and mTor pathways inside the cell.
'''IGF1R''' is a transmembrane protein receptor. It is composed of two alpha subunits and two tyrosine beta subunits. Both alpha subunits are cysteine-rich region and therefore linked with a disulfide bond. Ligand-binding on alpha subunit induces activation of beta subunit by autophosphorylation. It further leads to activation of the Akt and mTor pathways inside the cell.


Due to their homology sequences, the three members of the insulin protein family: IGF1, IGF2 and Insulin can interact with one another of the different receptors. Hence, Insulin binds to IGF1R following the same mechanism and activated the intracellular pathways in the same way IGF1 does.
Due to their homology sequences, the three members of the insulin protein family: IGF1, IGF2 and Insulin can interact with one another of the different receptors. Hence, Insulin binds to IGF1R following the same mechanism and activated the intracellular pathways in the same way IGF1 does.
Therefore, the various concentration of the insulin proteins regulates the cell activity in different context, for instance in excess of glucose or lack of Growth Hormone.
Therefore, the various concentration of the insulin proteins regulates the cell activity in different context, for instance in excess of glucose or lack of Growth Hormone.
<Structure load='1wqj' size='250' frame='true' align='left' caption='Insert caption here' scene='Insert optional scene name here' />




=== Inhibiting interaction : IGF1 - IGFBP ===
=== Inhibiting interaction : IGF1 - IGFBP ===
'''IGF binding proteins''' ('''IGFBPs''') weight 24 to 45 kDa. All six IGFBPs share 50% homology with each other and have binding affinities at the same order of magnitude for IGF1 and IGF2 but have greater affinities then IGF1 for its receptor. Once IGF1 is bound to Insulin-like Growth Binding Protein (IGFBP), IGF1 cannot be linked to IGF1R any longer. Therefore, increases in serum levels of this IGFBP result in a decrease of IGF1 activity thus inhibiting the cellular pathways.
'''IGF binding proteins''' ('''IGFBPs''') weight 24 to 45 kDa. All six IGFBPs share 50% homology with each other and have binding affinities at the same order of magnitude for IGF1 and IGF2 but have greater affinities then IGF1 for its receptor. Once IGF1 is bound to Insulin-like Growth Binding Protein (IGFBP), IGF1 cannot be linked to IGF1R any longer. Therefore, increases in serum levels of this IGFBP result in a decrease of IGF1 activity thus inhibiting the cellular pathways.


The IGFBPs help to lengthen the half-life of circulating IGFs in all tissues. That is why approximately 98% of IGF1 exists as complexed form with one of the six different IGFBP. '''IGFBP3''', the most abundant protein, accounts for 80% of all IGF binding. Inside the liver, this mechanism is responsible for positive feedback, more precisely it allows growth hormone to continuously act upon the liver to produce more IGF1.
The IGFBPs help to lengthen the half-life of circulating IGFs in all tissues. That is why approximately 98% of IGF1 exists as complexed form with one of the six different IGFBP. '''IGFBP3''', the most abundant protein, accounts for 80% of all IGF binding. Inside the liver, this mechanism is responsible for positive feedback, more precisely it allows growth hormone to continuously act upon the liver to produce more IGF1.




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=== Biological context ===
=== Biological context ===


[[Image:Biologic context.gif]]
[[Image:Biologic context.gif|right]]




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On the contrary, a lower IGF1 is associated with an increased risk to develop an '''Alzheimer disease'''. According to this other trial, IGF1 higher levels may protect against subclinical and clinical neurodegeneration.<ref>Westwood AJ, Beiser A, et all, Neurology, 2014 May, 6;82(18):1613-9</ref>
On the contrary, a lower IGF1 is associated with an increased risk to develop an '''Alzheimer disease'''. According to this other trial, IGF1 higher levels may protect against subclinical and clinical neurodegeneration.<ref>Westwood AJ, Beiser A, et all, Neurology, 2014 May, 6;82(18):1613-9</ref>


</StructureSection>
== References ==
== References ==
<references/>
<references/>

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