Biology and Pathology of the Endocrine Pancreas, Université de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, France.
Regulation of Glycemia by Central Nervous System, Université de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, France.
Biomolecules. 2020 Jul 16;10(7):1057. doi: 10.3390/biom10071057.
Type 2 diabetes (T2D) occurs by deterioration in pancreatic β-cell function and/or progressive loss of pancreatic β-cell mass under the context of insulin resistance. α7 nicotinic acetylcholine receptor (nAChR) may contribute to insulin sensitivity but its role in the pathogenesis of T2D remains undefined. We investigated whether the systemic lack of α7 nAChR was sufficient to impair glucose homeostasis.
We used an α7 nAChR knock-out (α7) mouse model fed a standard chow diet. The effects of the lack of α7 nAChR on islet mass, insulin secretion, glucose and insulin tolerance, body composition, and food behaviour were assessed in vivo and ex vivo experiments.
Young α7 mice display a chronic mild high glycemia combined with an impaired glucose tolerance and a marked deficit in β-cell mass. In addition to these metabolic disorders, old mice developed adipose tissue inflammation, elevated plasma free fatty acid concentrations and presented glycolytic muscle insulin resistance in old mice. Finally, α7 mice, fed a chow diet, exhibited a late-onset excessive gain in body weight through increased fat mass associated with higher food intake.
Our work highlights the important role of α7 nAChR in glucose homeostasis. The constitutive lack of α7 nAChR suggests a novel pathway influencing the pathogenesis of T2D.
2 型糖尿病（T2D）是在胰岛素抵抗的情况下，胰腺β细胞功能恶化和/或胰腺β细胞数量进行性丧失引起的。α7 型烟碱型乙酰胆碱受体（nAChR）可能有助于胰岛素敏感性，但它在 T2D 发病机制中的作用仍未确定。我们研究了全身缺乏α7 nAChR 是否足以损害葡萄糖稳态。
我们使用了一种α7 nAChR 敲除（α7）小鼠模型，该模型喂食标准的普通饲料。体内和体外实验评估了缺乏α7 nAChR 对胰岛质量、胰岛素分泌、葡萄糖和胰岛素耐量、身体成分和食物行为的影响。
年轻的α7 小鼠表现出慢性轻度高血糖，伴有葡萄糖耐量受损和β细胞数量明显减少。除了这些代谢紊乱外，老年小鼠还出现了脂肪组织炎症、血浆游离脂肪酸浓度升高以及老年小鼠的糖酵解肌肉胰岛素抵抗。最后，喂食普通饲料的α7 小鼠通过增加与高食物摄入相关的脂肪量，出现了体重的迟发性过度增加。
我们的工作强调了α7 nAChR 在葡萄糖稳态中的重要作用。α7 nAChR 的组成性缺乏提示了影响 T2D 发病机制的新途径。
