Objective
Tobacco abuse elevates the risk of developing type 2 diabetes (T2D). This effect is attributed to nicotine, the major addictive compound in cigarettes and chewing tobacco. Nicotine acutely activates nicotinic receptors (nAchRs) while extended exposure results in receptor desensitization. Accumulating evidence suggests that long-term exposure to nicotine impairs beta cell function. Recent results (host laboratory) demonstrate that nicotine acutely modulates insulin secretion and that reduced nAchR expression in beta cells results in an increased risk for developing T2D. This suggests that activation of nAchRs is critical for beta cell function. However, the precise mechanisms to modulate beta cell function upon long-term exposure to nicotine in healthy and metabolically compromised conditions, have not been determined yet.
NACHO will investigate the effects of nicotine on insulin secretion using MafA mutant animals (model for beta cell dysfunction lacking specific nAchRs (Chrnb2/4)) and human islets. Molecular mechanisms by which nicotine affect insulin secretion will be studied by generating stable clones (CRISPR/Cas9) of human beta cells (EndoC-βH2) lacking CHRNB2/4 and evaluating cell signaling responses (calcium/sodium influx, exocytosis, plasma membrane potential) to nicotine/acetylcholine. The role of long-term nicotine exposure on beta cell adaptability will be assessed in diet-induced obese WT and MafA mutant mice treated with nicotine and evaluating beta cell function and proliferation in vivo (glucose tolerance) and ex vivo (insulin secretion and immunohistochemistry).
The clinical impact of specific nAchR gene risk alleles and nicotinic signaling on insulin secretion will be evaluated in non-diabetic humans. Understanding how nicotine influences beta cell function in diabetes development is of considerable clinical interest since tobacco abuse is common and smoking cessation therapy is widely used. NACHO will aid to develop personalized medicine.
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.
- natural sciences biological sciences cell biology cell signaling
- natural sciences chemical sciences inorganic chemistry alkali metals
- natural sciences chemical sciences inorganic chemistry alkaline earth metals
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences health sciences personalized medicine
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
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.
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.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2017
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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.
22100 Lund
Sweden
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.