Loss of melatonin signalling and its impact on circadian rhythms in mouse organs regulating blood glucose
| Autor: | Sabine Wolgast, Elena Gross, Eckhard Mühlbauer, Elmar Peschke, Karin Labucay |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Blood Glucose
Male endocrine system medicine.medical_specialty Circadian clock Biology Melatonin receptor Melatonin Islets of Langerhans Mice Internal medicine Insulin Secretion medicine Zeitgeber Animals Insulin Circadian rhythm RNA Messenger Sequence Deletion Pharmacology Metabolic Syndrome Mice Knockout Receptor Melatonin MT2 Receptor Melatonin MT1 Intracellular Signaling Peptides and Proteins Period Circadian Proteins Circadian Rhythm CLOCK Endocrinology Gene Expression Regulation Liver hormones hormone substitutes and hormone antagonists medicine.drug PER1 Signal Transduction |
| Zdroj: | European journal of pharmacology. 606(1-3) |
| ISSN: | 1879-0712 |
| Popis: | 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 MT(1) and MT(2) 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 RevErbalpha 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 MT(1), MT(2) or MT(1) and MT(2) 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. |
| Databáze: | OpenAIRE |
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