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Decorin : A new player in the communication between skeletal muscle and pancreatic beta- cell?

Research unit

EA 7294 - Diabète et thérapeutique : îlots pancréatiques et innovations technologiques (DIATHEC)
Centre européen d'étude du diabète, Bld Leriche 67200 Strasbourg

Group

Name: DIATHEC

Group leader: SIGRIST Séverine - s.sigrist@ceed-diabete.org

Group leader's phone: 0390201212

Website: Visit website

Group organization:
- Chercheurs: 5
- ITA: 5
- Doctorants: 4
- Post-Docs: 0
- Autres: 4

Publications of the team linked to the topic (3 last years):
1) IL-13 improves beta-cell survival and protects against IL-1beta-induced beta-cell death.
Rütti S, Howald C, Arous C, Dermitzakis E, Halban PA, Bouzakri K. Mol Metab. 2015 Nov 17;5(2):122-31.

2) Circulating Follistatin Is Liver-Derived and Regulated by the Glucagon-to-Insulin Ratio. Hansen JS, Rutti S, Arous C, Clemmesen JO, Secher NH, Drescher A, Gonelle-Gispert C, Halban PA, Pedersen BK, Weigert C, Bouzakri K, Plomgaard P. J Clin Endocrinol Metab. 2016 Feb;101(2):550-60.
3) Human skeletal myotubes display a cell-autonomous circadian clock implicated in basal myokine secretion. Perrin L, Loizides-Mangold U, Skarupelova S, Pulimeno P, Chanon S, Robert M, Bouzakri K, Modoux C, Roux-Lombard P, Vidal H, Lefai E, Dibner C. Mol Metab. 2015 Aug 6;4(11):834-45.

About PhD

PhD Director: SIGRIST Séverine - s.sigrist@ceed-diabete.org

Phone: 0390201212

Junior advisor: BOUZAKRI Karim

Co-tutely: non

Co-Director: non

About PhD topic :

Title: Decorin : A new player in the communication between skeletal muscle and pancreatic beta- cell?

Project: The description of the communication between the muscle and the pancreas was recently implemented by our research team. Thanks to a model in which pancreatic beta cells were treated with conditioned medium prepared from human primary myotubes, we have shown that factors secreted by the muscle (myokines) influence the survival and function of pancreatic beta cells. This interaction depends on the degree of insulin sensitivity in skeletal muscle. When the muscle responds properly to the insulin, the latter secretes myokines that have a positive effect on pancreatic beta cells (increased proliferation and insulin secretion in response to glucose). However, if the muscle is insulin resistant, other factors are secreted and negatively impact on the pancreatic beta cells survival and function. This resistance to insulin exchange muscle secretion profile which in turn has a deleterious effect on the pancreas. The aim of this project is to define the mechanisms of action in vitro and in vivo of new MYOKINE, decorin.

Decorin is a biologically active component of the extracellular matrix (ECM) with a ubiquitous tissue distribution, found in a variety of connective tissues such as skin , tendons , bones or cartilage55 . The gene encoding this protein is called DCN .
Thanks to a human in vitro model of skeletal muscle fiber type I and type II, we have recently demonstrated that skeletal muscle cells retain the fibrillar phenotype of the biopsies and that these cells have a unique signature in terms of myokines. In addition, the different myokines effect is due to the fibrillar composition of human skeletal cells and their state of insulin sensitivity. The myokines secreted by the triceps have a positive effect on the pancreatic beta cells in basal condition or in insulin resistance situation. Decorin is particularly increased in the triceps compared to the soleus. These data suggest that skeletal muscle cells developed from soleus and triceps secrete their own myokines profile. Thus, decorin is the cause positive effects on pancreatic beta cells conditioned medium obtained from myotubes triceps.

In our project, we want to define and characterize the mode of action of decorin in control situation and during the development of diabetes. For this we will:
- Demonstrate that decorin is regulated in vivo in humans by physical exercise confirming that it is a MYOKINE (Collaboration with CIM, Copenhagen , Denmark).
- Characterize the effect of decorine in vitro on pancreatic beta cells in control condition and after induction of inflammation ( CYTOMIX , conditioned medium insulin resistant) .
- Validate the biological efficacy of decorine in vivo in transgenic mice overexpressing decorin and in diabetic rats (Collaboration with University of Basel )

Wished skills: The candidate must have a profile at the interface between physiology and molecular biology. Additional experience in pharmacology is needed

Expertises which will be acquired during the training: This integrative physiology research project will allow the student to acquire a multidisciplinary profile physiology, cell biology, animal testing , molecular biology senior and proteomics . It will also give the opportunity to work with several international laboratory which will enable it to set up a collaborator network.