Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM Juriquilla, 3001 Boulevard Juriquilla, Juriquilla, Querétaro, cp 76230, Mexico.
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM Juriquilla, 3001 Boulevard Juriquilla, Juriquilla, Querétaro, cp 76230, Mexico.
Gen Comp Endocrinol. 2020 Sep 1;295:113477. doi: 10.1016/j.ygcen.2020.113477. Epub 2020 Mar 30.
Circadian phenomena rule many activities of life on earth. Disruptions in circadian rhythmicity and rhythms have been recognized as a contributing factor for diseased states, for instance metabolic disruptions like diabetes. Diabetes develops as a consequence of faulty insulin pathway signaling, either by lack of insulin production (diabetes type I), or by loss of responsiveness in target tissues (diabetes type 2). In this work we use the model organism Drosophila melanogaster with three different mutant hypomorphic conditions at different levels of the insulin pathway. The insulin pathway is a very evolutionarily conserved pathway. We study these different diabetic conditions as a source of circadian rhythm abnormalities and circadian-related co-morbidities. We do so by studying circadian rhythmicity, activity, sleep and sleep structure, and feeding behavior. Results show that flies with impaired insulin signaling show circadian rhythm and rhythmic-related co-morbidities, especially female flies, as a consequence of the diabetic state. The most extreme disruptions occur in flies with impaired insulin receptor signaling, which stands at the beginning of the insulin pathway, in principle affecting most if not all aspects of this pathway. Our work shows that defective insulin signaling is a source of circadian rhythm and rhythmic related co-morbidities.
昼夜节律现象主宰着地球上许多生命活动。昼夜节律的紊乱和节奏失调已被认为是疾病状态的一个促成因素，例如代谢紊乱，如糖尿病。糖尿病的发生是由于胰岛素通路信号传导的缺陷，要么是由于胰岛素产生不足（1 型糖尿病），要么是由于靶组织对胰岛素的反应丧失（2 型糖尿病）。在这项工作中，我们使用了不同水平胰岛素通路的三种不同的突变弱表型条件的模式生物果蝇。胰岛素通路是一种非常进化保守的通路。我们研究这些不同的糖尿病条件，作为昼夜节律异常和与昼夜节律相关的合并症的来源。我们通过研究昼夜节律性、活动、睡眠和睡眠结构以及进食行为来做到这一点。结果表明，胰岛素信号转导受损的果蝇表现出昼夜节律和与节律相关的合并症，尤其是雌性果蝇，这是由于糖尿病状态的结果。最极端的干扰发生在胰岛素受体信号转导受损的果蝇中，这处于胰岛素通路的开始，原则上影响该通路的大多数（如果不是全部）方面。我们的工作表明，胰岛素信号转导的缺陷是昼夜节律和与节律相关的合并症的一个来源。
