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Cellular and molecular mechanisms of pancreatic beta-cell adaptation to pregnancy in large mammals.

Objective

Pregnancy is characterized by the development of maternal insulin resistance and increased hepatic glucose production to provide sufficient glucose to be used as nutrient by the developing fetus. The maternal insulin-producing beta-cells expand to counterbalance the increased glucose levels and failure of this process can lead to development of gestational diabetes, which has great health implications for both the mother and the developing fetus. Yet, our knowledge on the mechanisms behind the pregnancy-induced beta-cell expansion in humans is limited. To address this knowledge gap, in the betaPPreg project, I will use the pig model as an ideal surrogate large mammal to study the mechanisms and identify physiological drivers of pregnancy-induced beta-cell expansion. First, I will identify the extent and the different cellular mechanisms of beta-cell adaptation in the porcine pancreas over the three trimesters of gestational time (~114 days) by histological analysis. To reveal the physiological candidates of beta-cell adaptation, I will perform untargeted metabolomics coupled with proteomics analysis of serum and pancreas at sequential temporal windows during gestation. This analysis will point to the significantly changed metabolites and growth factors that can be potentially involved in beta-cell expansion. I will perform a small-scale metabolite/growth factor screen in isolated neonatal porcine islets with the most regulated factors, to causatively link the metabolites/growth factors stimulating beta-cell expansion. The most promising candidates will be then tested in isolated human islets and human-derived ductal organoids to assess their translational potential as beta-cell proliferation/differentiation inducers and human therapeutics. Overall, the proposed project will greatly advance our understanding of beta-cell adaptation during pregnancy in large mammals and provide novel therapeutic candidates for gestational diabetes treatment.

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Keywords

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Programme(s)

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Topic(s)

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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.

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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

(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 173 847,36
Address
INGOLSTADTER LANDSTRASSE 1
85764 Neuherberg
Germany

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Region
Bayern Oberbayern München, Landkreis
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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