IGF1: Difference between revisions
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=== 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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insulin receptor), IGF1 activates a signalling cascade by autocrine or paracrine way resulting in cell '''growth''', '''proliferation''' and '''survival against apoptose'''. | insulin receptor), IGF1 activates a signalling cascade by autocrine or paracrine way resulting in cell '''growth''', '''proliferation''' and '''survival against apoptose'''. | ||
However IGFBPs can activate or inhibate IGF1 actions on their target cells.<ref>http://www.hal.inserm.fr/tel-00932409/, 26/01/2017</ref> <ref>Elena Conti, Maria Beatrice Musumeci, et all, IGF-1 and atherothrombosis: relevance to pathophysiology and therapy,Clinical Science, May 01, 2011, 120 (9) 377-402</ref> | However IGFBPs can activate or inhibate IGF1 actions on their target cells.<ref>http://www.hal.inserm.fr/tel-00932409/, 26/01/2017</ref> <ref>Elena Conti, Maria Beatrice Musumeci, et all, IGF-1 and atherothrombosis: relevance to pathophysiology and therapy,Clinical Science, May 01, 2011, 120 (9) 377-402</ref> | ||
If IGF1 is lacking, it reduces cell growth and can also induce dysfunctions or even apoptose of cells, thus creating | If IGF1 is lacking, it reduces cell growth and can also induce dysfunctions or even apoptose of cells, thus creating diseases. | ||
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Knowing that IGF1 leads to cell proliferation with apoptose inhibition, if DNA undergoes alterations or mutations, those alterated cells will proliferate and survive even though it should result in their elimination by apoptose. Hence inducing '''cancer proliferation'''. <ref>R. Kaaks, Médecine Nucléaire - Imagerie fonctionnelle et métabolique, 2003, vol.27, n°1</ref> | Knowing that IGF1 leads to cell proliferation with apoptose inhibition, if DNA undergoes alterations or mutations, those alterated cells will proliferate and survive even though it should result in their elimination by apoptose. Hence inducing '''cancer proliferation'''. <ref>R. Kaaks, Médecine Nucléaire - Imagerie fonctionnelle et métabolique, 2003, vol.27, n°1</ref> | ||
'''The Laron syndrom''', caused by mutation of GH genes, features growth failure and high insulin sensibility. Thus reducing concentration of GH receptors and inducing an IGF1 low level. Treatment is based on biosynthetic IGF1 carry out in mecasermin (a drug developed by Genentech) with IGFBP3 and recombinant human IGF1. One main side effect is hypoglycemia due to IGF1 activity. <ref>https://en.wikipedia.org/wiki/Laron_syndrome, 26/01/2017</ref> | |||
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Clinical trials with IGF1 injection on persons affected by '''diabetes type I and II''', brought to light an improvement of glycemic control and a reduction of insulin injection necessarly to keep a normal glycemic regulation. But due to side effects such as pain, this treatment was interrupted until recently, with the introduction of an IGF1 and IGFBP3 combination, clinical trials seemed to display the same results as previously, nevertheless with reduced side effects. <ref>Richard Holt, Diabetes Voice, Septembre 2003, Volume 48, Numéro 2</ref> | Clinical trials with IGF1 injection on persons affected by '''diabetes type I and II''', brought to light an improvement of glycemic control and a reduction of insulin injection necessarly to keep a normal glycemic regulation. But due to side effects such as pain, this treatment was interrupted until recently, with the introduction of an IGF1 and IGFBP3 combination, clinical trials seemed to display the same results as previously, nevertheless with reduced side effects. <ref>Richard Holt, Diabetes Voice, Septembre 2003, Volume 48, Numéro 2</ref> | ||
Other clinical trials have shown higher IGF1 levels for patients with | Other clinical trials have shown higher IGF1 levels for patients with Parkinson advanced diseases, it doesn’t occur clear enough at early stages, compared to healthy persons. Nevertheless, the relationship between IGF1 levels and '''Parkinson disease''' duration or severity stays uncertain. That is why this trial concludes to an IGF1 limited prediction marker in Parkinson disease even if it could be a biomarker more pronounced in advanced stage illness. <ref>Srinivas Teppala, Anoop Shankar, Diabetes Care, Octobre 2010, Volume 33, Number 10</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> | 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> | ||