Objective
Type 2 diabetes mellitus (T2DM) is a complex genetic disorder of largely obscure etiology where alleles at numerous loci are thought to interact with environmental and stochastic cues to induce the phenotype. We have recently identified a T2DM susceptibility allele at the DKK3 locus. Using a combination of case/control association and functional studies, we demonstrated that the minor allele of SNP rs11022111 in the DKK3 promoter is significantly associated with T2DM in two Chinese and one Caucasian cohort and results in the disruption of a conserved SP1 binding site, leading to reduced DKK3 expression. We also showed that, in contrast to other members of the DKK family, DKK3 is a likely agonist of Wnt signaling (both canonical and non-canonical), in a Fz- and LRP6-dependent manner and regulates the expression of TCF7L2, another T2DM susceptibility gene. Our preliminary data implicate the regulation of Wnt signaling in the pathogenesis of T2DM. In this proposal, we hypothesize that aberrant Wnt signaling in the adult pancreas can lead to impaired glucose tolerance, insulin secretion and other diabetic phenotypes. To address how Dickkopf 3 influences Wnt signaling in β-cells and pancreatic islets as well as pancreatic islet functions, I propose to identify the subset of Wnt signaling components that are active in MIN6 cells and islets, to characterize the effect of impaired Wnt signaling on islet function and formation, and finally, to investigate the metabolic state of Dkk3-/- mice when challenged with a high fat diet.
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.
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.
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences health sciences nutrition
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Programme(s)
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Topic(s)
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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.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2010-RG
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Funding Scheme
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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.
Coordinator
171 77 STOCKHOLM
Sweden
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