IGF1: Difference between revisions

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Maxime Julliot, Virginie Nakad, Alexia Kindler, Michal Harel, Alexander Berchansky

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 == Metabolism ==
 === Biological context ===
 [[Image:Biologic context.gif]]
-Secretion of GH induces IGF1 transcription but IGF1 can also be secreted by
-the liver without GH stimulation. After binding to its receptors (IGF1R and
-insulin receptor), IGF1 activates a signalling cascade by autocrine or paracrine
+Secretion of GH induces IGF1 transcription but IGF1 can also be secreted by the liver without GH stimulation. After binding to its receptors (IGF1R and
-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 diseases.
 === Related diseases ===
 Growth failure, diabetes, cardiovascular pathology and others diseases such as Laron syndrom or cancers can be the consequences of an IGF1 low level.
-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></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></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>
 == Applications ==
-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></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 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 most pronounced in advanced stage disease. <ref></ref>
+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></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>