Lu dans le livre des résumés des présentations faites lors du congrès "13éme journées de la Société Française de Myologie SFM" tenu à l'Ecole Normale Supérieure de Lyon les 23-24 & 25 Novembre 2015 http://www.congresjsfm.org/?q=fr/node/15
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Acetylcholine Receptor (AChR) antibodies cause alterations of glucose homeostasis in Myasthenia Gravis (MG) models
Marie Maurer, Mohamed Attia, Marieke Robinet, Gillian Butler-Browne, Sonia Berrih-Aknin
Research unit CNRS FRE3617/INSERM U974/ Sorbonne Universités, UPMC Univ Paris 06, UM76/AIM - Institute of Myology - Therapies of the disorders of striated muscle Pitié-Salpêtrière, Paris, France.
Myasthenia Gravis (MG) is an autoimmune disease in which most patients have antibodies targeting post-‐synaptic proteins. Clinical features comprise muscle weakness and fatigability, which are attributed to neuromuscular junction defects. However, little is known about muscle physiology in MG, although it is now accepted that muscle is not a passive target.
Muscle is a major insulin-‐dependent organ that uses and stocks large amounts of glucose and thus participates in glucose homeostasis. We previously described a decrease of Akt phosphorylation by insulin in the presence of AChR antibodies in muscle cells. Akt pathway is involved in insulin-‐mediated glucose uptake, so we investigated this aspect in
In mouse experimentally induced autoimmune myasthenia gravis (EAMG), we performed a glucose tolerance test, evaluating glycaemia at regular intervals after an injection of glucose in overnight fasted mice. In EAMG mice, the glycaemia peaked higher than in control mice at 30min post-‐injection, then decreased faster, so that in the next intervals, the glycaemia of both groups were the same. We also measured insulin in the serum during this test at 0 and 75min. Insulin levels were the same in fasted mice, but were higher in EAMG at 75min (p< 0,02). These results evoke an insulin resistance. Preliminary results also suggest that anti-‐AChR antibodies would be sufficient to decrease glucose capture of muscle cells in vitro, so that this metabolic phenotype could be generated from a muscle insulin resistance.
Insulin resistance is the main feature of the metabolic syndrome, also known as pre-diabetes. It has also been described as inversely correlated to muscle force. Thus, insulin resistance could participate in the pathogenesis in MG and therapies aiming at improving glucose capture could complement existing treatments.