Wnt agonist Dickkopf 3 (DKK3) is a type 2 diabetes susceptibility gene

Projektinformationen

DKK3 T2DM

ID Finanzhilfevereinbarung: 268397

Abgeschlossenes Projekt

Startdatum 1 September 2010

Enddatum 31 August 2013

Finanziert unter

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Gesamtkosten € 75 000,00

EU-Beitrag € 75 000,00

Koordiniert durch

KAROLINSKA INSTITUTET
Sweden

Ziel

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.

Wissenschaftliches Gebiet

• medical and health sciences › clinical medicine › endocrinology › diabetes
• medical and health sciences › health sciences › nutrition

Programm/Programme

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Thema/Themen

• FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants"

Aufforderung zur Vorschlagseinreichung

FP7-PEOPLE-2010-RG
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

MC-IRG - International Re-integration Grants (IRG)

Koordinator

KAROLINSKA INSTITUTET

Kontakt Verwaltung

Per-Olof Berggren (Prof.)

• EU-Beitrag: € 75 000,00
• Adresse: Nobels Vag 5 ; 17177 Stockholm ; Schweden
• Region: Östra Sverige › Stockholm › Stockholms län
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: Keine Daten