Post-doctoral position : Screening of novel molecules interacting with amine oxidases for discovery of anti-diabetic or anti-obesity drugs

Obesity and diabetes are currently increasing, in spite of the numerous public health campaigns and interventions. Alongside the nutritional and lifestyle improvement advices, the interest of novel therapeutic approaches have to limit the global epidemics of diabetes and obesity. The therapeutic approaches (pharrmacologic or surgical) currently available can be improved by the discovery of novel agents. In this context, adipose tissue plays an important role in both diabetes and obesity : it stores excessive energy intake and participates to glucose handling and body mass regulation, via the adipokines it secretes. We have shown that an enzyme,« semicarbazide-sensitive amine oxidase» (SSAO), is highly expressed in adipocytes and generates hydrogen peroxide when oxidizing biogenic or exogenous amines. Such member of the reactive oxygen species family, mimic several insulin actions. Hydrogen peroxide is involved in the insulin-like actions of benzylamine (a SSAO-substrate) in vitro : glucose uptake stimulation and lipolysis inhibition. When orally administered, benzylamine is also able, to alleviate hyperglycaemia in diabetic mice. On the oppposite, chronic treatment of obese rodents with SSAO inhibitors limits body weight gain and/or adipose depot accumulation.

The post-doctoral position consists in investigating the insulin-like effect of novel SSAO substrates, more powerful than benzylamine. Such molecules will be obtained by high-throughput screening or by computer-assisted design of docking to the amine oxidase catalytic site. The insulin-like effects have to be evidenced in fat cells in vitro, and after chronic administration in mice. The novel inhibitors will be also tested on the same models to detect ther putative anti-obesity or anti-inflammatory properties. The candidate must possess basic knowledge in pharmacology, especially on « oxidative stress » and on « insulin action », and must be able to perform experiments on cells and laboratory rodents.

The stay is one-year long, in team 3 Inserm unit 858 in Toulouse within the DIOMED project (http://diomed-sudoe.eu).

The person to contact is :

Carpéné Christian
NSERM U 858
Institut de Médecine Moléculaire de Rangueil
Equipe sécrétions adipocytaires, obésité et pathologies associées
IFRBMT Université Paul Sabatier Toulouse III

Post : INSERM U 858 - I2MR, Eq n°3
CHU Rangueil, Bat. L4, BP 84225, 31432 TOULOUSE Cedex 4, France
email: Christian.Carpene@inserm.fr
web1: adipolab.weebly.com
web2: http://diomed-sudoe.eu
web3: http://obesitydiabetesinctp.weebly.com