NOVEL PREP1-DEPENDENT TRANSCRIPTIONAL NETWORKS IN THE CONTROL OF INSULIN SENSITIVITY

Objective

Type 2 diabets and obesity are related conditions representing major components of the metabolic syndrome and one of the most challenging health problems of this century, also because of their growing impact in childhood. Different studies have identified PPAR-gamma coactivator-1 (PGC-1alpha) as a relevant type 2 diabetes susceptibility gene playing an important role in human obesity as well. Subsequent investigations led to the discovery that p160MBP (MybBindingProtein) serves as a PGC-1alpha inhibitor. More recently, we showed that p160MBP is controlled by the Prep1 gene. Prep1 hypomorphic mice feature increase sensitivity to insulin due to raised PGC-1 alpha and decreased p160MBP levels. These mice also exhibit decreased fat body mass. Indeed, we also identified Prep1 in genetic screenings in C. Elegans and mouse ,as a major gene involved in energy homeostasis and obesity. Importantly, we have preliminary data showing Prep1 overexpression in euglycemic first-degree relatives of type 2 diabetics, which are at very high risk of diabetes. This project aims at understanding how Prep1 gene controls insulin sensitivity and determines adipogenesis, obesity and type 2 diabetes in humans. We will: 1: elucidate the molecular basis of Prep1 role in insulin sensitivity and adipogenesis through in vitro and animal model studies; 2: assess the significance of Prep1 function to insulin sensitivity in humans and the role of this gene in type 2 diabetes and its subphenotypes and in other components of the metabolic syndrome; 3: identify Prep1 target genes and establish their potential as targets for novel strategies to treat type 2 diabetes and metabolic syndrome. To achieve these objectives we have built a multidisciplinary network and gathered experts in the Prep1/p160MBP signaling, type 2 diabetes and obesity molecular biology and genetics, human and mouse genetics and high throughput analysis of gene expression and identification of target genes.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

• natural sciences biological sciences genetics
• medical and health sciences clinical medicine endocrinology diabetes
• medical and health sciences basic medicine physiology homeostasis
• medical and health sciences health sciences nutrition obesity
• natural sciences biological sciences molecular biology

Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

• Prep1
• glucose tolerance
• insulin resistance
• metabolic syndrome
• p160 myb-binding-protein
• type-2 diabetes

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-HEALTH - Specific Programme "Cooperation": Health

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• HEALTH-2007-2.4.3-3 - Insulin resistance as a key factor in the development of diabetes and metabolic syndrome

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-HEALTH-2007-A
See other projects for this call

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

CP-FP - Small or medium-scale focused research project

Coordinator

Participants (4)