cousineg
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Le Gleevec (Imatinib) peut traiter le diabète du type 1???

mer. nov. 19, 2008 5:22 am

On a découvert chez des souris que le Gleevec (Imatinib) peut traiter le diabète de type 1. :hallucine:

Voir l'article du 17/11/2008 :

http://www.ecancermedicalscience.com/ne ... itemId=349

'A new study by Cédric Louvet and colleagues reveals that imatinib (Gleevec) and another tyrosine kinase-inhibiting drug prevented or reversed type 1 diabetes in mice by dampening the animals' immune system.'

:debile:

cousineg
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Re: Le Gleevec (Imatinib) peut traiter le diabète du type 1?

mar. mars 30, 2010 4:08 pm

Cancer drug reverses diabetes in mice
''A drug developed to treat leukemia also reverses diabetes in a mouse model of the disease. A new study by Cédric Louvet and colleagues reveals that imatinib (Gleevec®) and another tyrosine kinase-inhibiting drug prevented or reversed type 1 diabetes in mice by dampening the animals' immune system. Imatinib was developed to inhibit a specific tyrosine kinase present in chronic myelogenous leukemia, but the drug also inhibits other tyrosine kinases, several of which exist in the immune system. Type 1 diabetes is an autoimmune disorder, caused when inflammation destroys cells in the pancreas. To test if imatinib would ameliorate this inflammation and thus prevent onset of the diabetes, the researchers tested the drug in a mouse model of the disease. In doing so, they found that treating mice with imatinib or a similar inhibitor drug for seven weeks before the onset of autoimmune (type 1) diabetes prevented development of the disease long after the treatment was stopped. The drug also put 80 percent of mice with existing disease into remission when mice were treated for 8-10 weeks after disease onset. The efficacy suggests that the same drugs that had important ramifications for cancer treatment could be used to treat type 1 diabetes and, possibly, other autoimmune diseases, according to the authors.
ARTICLE #08-10246 "Tyrosine kinase inhibitors reverse type 1 diabetes in NOD mice," by Cédric Louvet, Gregory L. Szot, Jiena Lang, Michael R. Lee, Nicolas Martinier, Gideon Bollag, Shirley Zhu, Arthur Weiss, and Jeffrey A. Bluestone
MEDIA CONTACT: Jeffery Bluestone, University of California-San Francisco Diabetes Center, San Francisco, CA; tel: 415-514-1683; e-mail: jbluest@diabetes.ucsf.edu''

Extrait de http://chinese.eurekalert.org/en/pub_re ... 111408.php

Two cancer drugs prevent, reverse type 1 diabetes, UCSF study shows
''Two common cancer drugs have been shown to both prevent and reverse type 1 diabetes in a mouse model of the disease, according to research conducted at the University of California, San Francisco. The drugs – imatinib (marketed as Gleevec) and sunitinib (marketed as Sutent) – were found to put type 1 diabetes into remission in 80 percent of the test mice and work permanently in 80 percent of those that go into remission''
Extrait de http://news.ucsf.edu/releases/cancer-dr ... -diabetes/

Cancer drug reverses diabetes in mice

http://www.ecancermedicalscience.com/ne ... itemId=349

Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice

http://en.scientificcommons.org/46144867

Cancer drug for diabetes

http://www.nhs.uk/news/2008/11November/ ... gtest.aspx

cousineg
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Re: Le Gleevec (Imatinib) peut traiter le diabète du type 1?

dim. mai 09, 2010 7:21 pm

Glivec: a new therapeutic opportunity for diabetes? 19 mai 2009
'So, back to diabetes. First, the animal model results are not the first to associate imatinib with a therapeutic effect in diabetic conditions. Some years ago, the drug was found to improve fasting glucose levels in diabetic CML patients. Second, the observation that imatinib also improves type II diabetes, suggest that the mechanism involved could be shared between the two conditions (type I and type II). One possibility is that the drug counteracts diabetes by maintaining ß-cell function by promoting a state similar to ischaemic preconditioning, and involving (among other things) NF-{kappa}B activation. Interestingly, the protective effect of imatinib was shared by sunitinib, which possesses a quite different profile of tyrosine kinase inhibitory activities. Sunitinib is a multi-targeted receptor tyrosine kinase inhibitor that is approved for the treatment of renal cell carcinoma and imatinib-resistant GIST. Its mechanism involves inhibition of PDGF-R and c-kit but not bcr-abl.'
Extrait de http://numedicus.co.uk/blog/?p=1

cousineg
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Re: Le Gleevec (Imatinib) peut traiter le diabète du type 1?

dim. mai 09, 2010 7:26 pm

Imatinib mesylate reduces endoplasmic reticulum stress and induces remission of diabetes in db/db mice. Février 2009
'OBJECTIVE: Imatinib has been reported to induce regression of type 2 diabetes in chronic leukemia patients. However, the mechanism of diabetes amelioration by imatinib is unknown, and it is uncertain whether imatinib has effects on type 2 diabetes itself without other confounding diseases like leukemia. We studied the effect of imatinib on diabetes in db/db mice and investigated possible mechanism's underlying improved glycemic control by imatinib. RESEARCH DESIGN AND METHODS: Glucose tolerance and insulin tolerance tests were done after daily intraperitoneal injection of 25 mg/kg imatinib into db/db and C57BL/6 mice for 4 weeks. Insulin signaling and endoplasmic reticulum stress responses were studied by Western blotting. beta-Cell mass and apoptotic beta-cell number were determined by combined terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and insulin immunohistochemistry. The in vitro effect of imatinib was studied using HepG2 cells. RESULTS: Imatinib induced remission of diabetes in db/db mice and amelioration of insulin resistance. Expression of endoplasmic reticulum stress markers in the liver and adipose tissues of db/db mice, such as phospho-PERK, phospho-eIF2alpha, TRB3, CHOP, and phospho-c-Jun NH(2)-terminal kinase, was reduced by imatinib. Insulin receptor substrate-1 tyrosine phosphorylation and Akt phosphorylation after insulin administration were improved by imatinib. Serum aminotransferase levels and hepatic triglyceride contents were decreased by imatinib. Pancreatic beta-cell mass was increased by imatinib, accompanied by decreased TUNEL(+) beta-cell and increased BrdU(+) beta-cell numbers. Imatinib attenuated endoplasmic reticulum stress in hepatoma cells in vitro. CONCLUSIONS: Imatinib ameliorated endoplasmic reticulum stress and induced remission of diabetes in db/db mice. Imatinib or related compounds could be used as therapeutic agents against type 2 diabetes and metabolic syndrome'
Extrait de http://www.citeulike.org/user/guhjy/article/3955732

cousineg
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Re: Le Gleevec (Imatinib) peut traiter le diabète du type 1?

dim. mai 09, 2010 7:35 pm

Soigner le cancer, et… guérir le diabète ?
La leucémie myéloïde chronique est une maladie acquise liée à une transformation néoplasique des cellules souches hématopoïétiques. Elle résulte d'une translocation entre les chromosomes 9 et 22. Une des conséquences moléculaires de cette translocation est la production d'un gène de fusion (Bcr-Abl) dont le produit est une tyrosine kinase à activité non contrôlée. Il a été bien démontré que l'activité de cette kinase était nécessaire à l'apparition de la maladie. Une stratégie visant à développer des inhibiteurs de Bcr-Abl a conduit à l'identification d'un dérivé du 2-phénylaminopyrimidine baptisé imatinib [1]. Ce composé inhibe l'activité Bcr-Abl et l'activité tyrosine kinase du récepteur du PGDF (platelet-derived growth factor). D. Veneri et al. [2] décrivent le cas du traitement par l'imatinib d'une malade atteinte de leucémie myéloïde chronique, mais également d'un diabète de type 2 diagnostiqué huit ans auparavant, et nécessitant depuis quatre ans un traitement par l'insuline. Deux mois après la mise en route du traitement à l'Imatinib, une rémission hématologique était apparente mais, de façon plus surprenante, les besoins en insuline étaient également fortement diminués allant jusqu'à un arrêt total du traitement par l'insuline cinq mois plus tard. La glycémie à jeun de la patiente était alors de 6,7 mmol/l et de 8,2 mmol/l deux heures après un test standardisé de tolérance au glucose. Les paramètres métaboliques suivis sur un an ont confirmé la disparition du diabète de type 2. Il est bien sûr très difficile de comprendre les raisons de cette spectaculaire régression du diabète d'autant plus que les auteurs ne précisent pas s'il s'agit d'une amélioration de la sensibilité à l'insuline, de la sécrétion de cette hormone ou des deux. La signalisation insulinique implique l'activation de nombreuses tyrosine kinases (le récepteur de l'insuline étant lui-même une tyrosine kinase) et la phosphorylation d'effecteurs très divers. L’imatinib agit-il sur la cascade de signalisation insulinique (ce qui semble contraire à l’intuition dans la mesure où il s'agit d'un inhibiteur des tyrosine kinases), sur l'une des étapes complexes de la sécrétion insulinique ou sur les mécanismes à la base même du diabète de type 2 tels que des phénomènes inflammatoires, de stress oxydant ou de lipotoxicité ? Il est trop tôt pour le dire. Cette étude illustre néanmoins le fait que, quel que soit le caractère maintenant très rationnel de la mise au point d'un médicament (identification de la cible, spécificité apparente, multiples études pré-cliniques et cliniques), il existe de bonnes (parfois) ou de mauvaises (souvent) surprises quant à son utilisation.
Extrait de http://www.edk.fr/reserve/revues/ms_ele ... =text.html

cousineg
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Re: Le Gleevec (Imatinib) peut traiter le diabète du type 1?

dim. sept. 16, 2012 6:10 am

"So, back to diabetes. First, the animal model results are not the first to associate imatinib with a therapeutic effect in diabetic conditions. Some years ago, the drug was found to improve fasting glucose levels in diabetic CML patients. Second, the observation that imatinib also improves type II diabetes, suggest that the mechanism involved could be shared between the two conditions (type I and type II). One possibility is that the drug counteracts diabetes by maintaining ß-cell function by promoting a state similar to ischaemic preconditioning, and involving (among other things) NF-{kappa}B activation. Interestingly, the protective effect of imatinib was shared by sunitinib, which possesses a quite different profile of tyrosine kinase inhibitory activities. Sunitinib is a multi-targeted receptor tyrosine kinase inhibitor that is approved for the treatment of renal cell carcinoma and imatinib-resistant GIST. Its mechanism involves inhibition of PDGF-R and c-kit but not bcr-abl.

On the face of it, the enlargement of the putative treatment population for imatinib from CML, which affects a few thousand people per year, to diabetes, which affects hundreds of millions of people, could have a dramatic effect on the commercial potential for Glivec™. However, a deeper analysis suggests this enlargement is unlikely to occur."
Extrait de http://numedicus.co.uk/blog/?p=1 Mai 2009

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