Dantas-Ferreira Rosana F, Raingard Helene, Dumont Stephanie, Schuster-Klein Carole, Guardiola-Lemaitre Beatrice, Pevet Paul, Challet Etienne
Circadian Clocks & Metabolism team Institute of Cellular and Integrative Neurosciences Centre National de la Recherche Scientifique (CNRS) University of Strasbourg Strasbourg France.
ADIR-SERVIER Research Group Suresnes France.
Endocrinol Diabetes Metab. 2018 Aug 31;1(4):e00039. doi: 10.1002/edm2.39. eCollection 2018 Oct.
Melatonin is a hormone synthesized mainly by the pineal gland, and secreted only at night. Melatonin has been proposed as a modulator of glucose metabolism.
Here we studied the metabolic effects of melatonin administration alone (s.c. 10 mg/kg) or in combination with metformin (p.o. 300 mg/kg), a widely used anti-diabetic drug. These treatments were tested on glucose tolerance, insulin sensitivity and food intake in Zucker fatty rats (i.e., bearing a missense mutation in the leptin receptor gene) and high-fat fed Sprague-Dawley rats.
Melatonin alone or in combination did not significantly modify glucose tolerance in either model. Melatonin alone in high-fat fed Sprague-Dawley improved insulin sensitivity to the level of metformin. In addition, combined treatment further ameliorated insulin sensitivity (+13%), especially during the late phase of rising glycemia. The lack of similar effects in Zucker rats suggests an involvement of leptin signaling in mediating the positive effects of melatonin. Body mass gain in Sprague-Dawley rats was decreased by both metformin, and combined metformin and melatonin. While melatonin alone did not markedly affect food intake, its combination with metformin led to a more pronounced anorexia (-17% food intake during the last week), as compared to metformin alone.
Melatonin improves the beneficial effects of metformin on insulin sensitivity and body mass gain in high-fat fed Sprague-Dawley rats. Therefore, the combination of melatonin and metformin could be beneficial to develop dual therapies to treat or delay type 2 diabetes associated with obesity.
褪黑素是一种主要由松果体合成且仅在夜间分泌的激素。褪黑素被认为是葡萄糖代谢的调节剂。
在此，我们研究了单独给予褪黑素（皮下注射10毫克/千克）或与二甲双胍（口服300毫克/千克，一种广泛使用的抗糖尿病药物）联合使用的代谢效应。在 Zucker 肥胖大鼠（即瘦素受体基因存在错义突变）和高脂喂养的Sprague-Dawley大鼠中，对这些处理在葡萄糖耐量、胰岛素敏感性和食物摄入量方面进行了测试。
单独使用褪黑素或联合使用在两种模型中均未显著改变葡萄糖耐量。在高脂喂养的Sprague-Dawley大鼠中，单独使用褪黑素可将胰岛素敏感性提高到二甲双胍的水平。此外，联合治疗进一步改善了胰岛素敏感性（提高13%），尤其是在血糖上升的后期。在 Zucker 大鼠中缺乏类似效应表明瘦素信号传导参与介导褪黑素的积极作用。二甲双胍以及二甲双胍与褪黑素联合使用均降低了Sprague-Dawley大鼠的体重增加。虽然单独使用褪黑素对食物摄入量没有明显影响，但其与二甲双胍联合使用导致厌食更为明显（最后一周食物摄入量减少17%），相比单独使用二甲双胍。
褪黑素可增强二甲双胍对高脂喂养的Sprague-Dawley大鼠胰岛素敏感性和体重增加的有益作用。因此，褪黑素与二甲双胍联合使用可能有利于开发治疗或延缓与肥胖相关的2型糖尿病的双重疗法。
