H2020Индивидуална стипендия2018–2020

NACHO · Nicotine actions on beta cell function in health and disease

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-06-01 → 2020-05-31
Финансиране от ЕС: 185 857 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Никотинът и влиянието му върху бета клетките в панкреаса се изследват чрез животински модели и човешки тъкани, за да се разбере как се променя секрецията на инсулин. Това помага да се установи връзката между тютюнозата и развитието на диабет тип 2.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Nicotine actions on beta cell function in health and disease

Tobacco abuse elevates the risk of developing type 2 diabetes. This effect has been recently attributed to nicotine, which is the major addictive compound in both cigarette smoke and chewing tobacco. Nicotine acutely activates its receptors while extended exposure results in receptors desensitization. Accumulating evidence suggests that long-term exposure to nicotine impairs pancreatic beta cell function. We have recently demonstrated that nicotine acutely modulates insulin secretion from pancreatic beta cells and that reduced expression of nicotinic receptors in beta cells results in an increased risk for developing type 2 diabetes. This suggests that activation of nicotinic receptors is critical for β-cell function. However, the precise mechanisms used by these receptors to modulate beta cell function upon long-term exposure to nicotine in healthy and metabolically compromised conditions have not been determined yet. Here we propose to investigate the effects of nicotine on insulin secretion using animal models and human islets. We will study the mechanisms by which nicotine affect insulin secretion in beta cells. Furthermore, we will assess the effects of long-term nicotine exposure on beta cell function in obese animals and the impact on insulin release in humans. Understanding how nicotine influences beta cell function in diabetes development is of considerable clinical interest since tobacco abuse is still common and nicotine treatment is widely used as smoking cessation therapy.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

LUNDS UNIVERSITET · LundКоординаторШвеция