Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 606, Issue 1-3, Pages 61-71Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2009.01.029
Keywords
Melatonin MT1- and MT2-receptors; Circadian rhythm; Insulin secretion; Glucose regulation; (Receptor knockout mouse)
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The transmission of circadian rhythms is mediated by specific promoter sequences binding a particular circadian clock factor. The pineal hormone melatonin acts via G-protein-coupled receptors to synchronise these clock-generated circadian rhythms. The study was aimed to elucidate the possible role of melatonin as a zeitgeber for peripheral clocks in pancreas and liver. Reverse transcription polymerase chain reaction (RT-PCR) provided evidence of the simultaneous expression of the melatonin receptors MT1 and MT2 in mouse pancreas, liver and hypothalamus. Melatonin receptor knockout mice were analysed with respect to the clock gene- or clock-output transcripts PER1, DBP and RevErb alpha in pancreas and liver, and both the occurrence of phase shifts and amplitude changes were detected. Circadian PER1 protein expression was found to be retained in melatonin receptor double knockout mice with an increased amplitude as measured by semiquantitative Western blot analysis. Moreover, an impact of melatonin receptor deficiency on insulin transcripts, and altered regulation of insulin secretion and glucose homeostasis were monitored in the knockout animals. Insulin secretion from isolated islets of melatonin receptor MT1, MT2 or mT(1) and MT2 double melatonin receptor-knockout animals was found to be increased relative to the wild type These data support the idea that melatonin synchronises the functions of the major organs involved in blood glucose regulation and negatively acts on the insulin secretion. (C) 2009 Elsevier B.V. All rights reserved.
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