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NACHO SIGNED

Nicotine actions on beta cell function in health and disease

Total Cost €

EC-Contrib. €

Partnership

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NACHO project word cloud

Explore the words cloud of the NACHO project. It provides you a very rough idea of what is the project "NACHO" about.

obese modulates cigarettes immunohistochemistry acetylcholine determined risk smoking compound desensitization medicine glucose function therapy crispr exocytosis adaptability expression dysfunction human mafa beta molecular impairs acutely clones secretion model nachr critical calcium personalized compromised mechanisms attributed diet considerable aid h2 t2d vivo humans stable alleles mutant receptors signaling activates host sodium activation plasma exposure ex extended suggests tolerance cas9 modulate generating abuse cell clinical insulin wt nicotine endoc proliferation effect nacho elevates tobacco accumulating influx influences nachrs animals cessation membrane precise lacking mice nicotinic chewing healthy laboratory metabolically chrnb2 cells diabetic receptor islets addictive diabetes gene

Project "NACHO" data sheet

The following table provides information about the project.

Coordinator	LUNDS UNIVERSITET Organization address address: Paradisgatan 5c city: LUND postcode: 22100 website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Sweden [SE]
Total cost	185˙857 €
EC max contribution	185˙857 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2017
Funding Scheme	MSCA-IF-EF-ST
Starting year	2018
Duration (year-month-day)	from 2018-06-01 to 2020-05-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	LUNDS UNIVERSITET LUNDS UNIVERSITET Organization address address: Paradisgatan 5c city: LUND postcode: 22100 website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	SE (LUND)	coordinator	185˙857.00

Map

Project 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.

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The information about "NACHO" are provided by the European Opendata Portal: CORDIS opendata.