Melatonin Signaling Controls the Daily Rhythm in Blood Glucose Levels Independent of Peripheral Clocks

• Published in: PloS one 2016-01, Vol.11 (1), p.e0148214
• Main Authors: Owino, Sharon, Contreras-Alcantara, Susana, Baba, Kenkichi, Tosini, Gianluca
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue - metabolism; Animal tissues; Animals; Biology and Life Sciences; Blood; Blood glucose; Blood Glucose - metabolism; Cellular signal transduction; Circadian rhythm; Circadian Rhythm - genetics; Circadian rhythms; CLOCK Proteins - genetics; CLOCK Proteins - metabolism; Cues; Diurnal; Gene expression; Gene Expression Regulation; Glucose; Glucose metabolism; Homeostasis; Insulin; Insulin resistance; Liver; Liver - metabolism; Male; Medicine and Health Sciences; Melatonin; Melatonin - metabolism; Melatonin receptors; Metabolism; Mice; Mice, Knockout; Muscle, Skeletal - metabolism; Muscles; Physiological aspects; Pineal gland; Pineal Gland - metabolism; Receptor, Melatonin, MT1 - deficiency; Receptor, Melatonin, MT1 - genetics; Receptor, Melatonin, MT2 - deficiency; Receptor, Melatonin, MT2 - genetics; Receptors; Retina; Retina - metabolism; Rhythm; Rodents; Signal Transduction; Signaling; Skeletal muscle
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0148214

Melatonin is rhythmically secreted by both the pineal gland and retina in a circadian fashion, with its peak synthesis occurring during the night. Once synthesized, melatonin exerts its effects by binding to two specific G-protein coupled receptors-melatonin receptor type 1(MT1) and melatonin receptor type 2(MT2). Recent studies suggest the involvement of MT1 and MT2 in the regulation of glucose homeostasis; however the ability of melatonin signaling to impart timing cues on glucose metabolism remains poorly understood. Here we report that the removal of MT1 or MT2 in mice abolishes the daily rhythm in blood glucose levels. Interestingly, removal of melatonin receptors produced small effects on the rhythmic expression patterns of clock genes within skeletal muscle, liver, and adipose tissue. Taken together, our data suggest that the loss of the daily rhythm in blood glucose observed in MT1(-/-) and MT2(-/-) mice does not occur as a consequence of 'disrupted' clocks within insulin sensitive tissues. Finally our results highlight a diurnal contribution of melatonin receptor signaling in the daily regulation of blood glucose levels.