Loss of melatonin signalling and its impact on circadian rhythms in mouse organs regulating blood glucose

Area of Science:

• Chronobiology
• Endocrinology
• Metabolism

Background:

• Circadian rhythms are synchronized by specific promoter sequences and the hormone melatonin.
• Melatonin acts via G-protein-coupled receptors to regulate circadian rhythms.
• The role of melatonin as a zeitgeber for peripheral clocks in the pancreas and liver requires elucidation.

Purpose of the Study:

• To investigate the role of melatonin as a zeitgeber for peripheral clocks in the pancreas and liver.
• To analyze the impact of melatonin receptor deficiency on clock gene expression and glucose homeostasis.

Main Methods:

• Reverse transcription polymerase chain reaction (RT-PCR) to detect melatonin receptor expression (MT1 and MT2) in mouse tissues.
• Analysis of melatonin receptor knockout mice for clock gene transcripts (PER1, DBP, RevErbalpha).
• Assessment of circadian PER1 protein expression via semiquantitative Western blot analysis.
• Monitoring of insulin transcripts, insulin secretion, and glucose homeostasis in knockout models.

Main Results:

• Melatonin receptors MT1 and MT2 are co-expressed in mouse pancreas, liver, and hypothalamus.
• Melatonin receptor knockout mice exhibited phase shifts and amplitude changes in clock gene expression.
• PER1 protein expression was retained but showed increased amplitude in double knockout mice.
• Melatonin receptor deficiency impacted insulin transcripts, insulin secretion, and glucose homeostasis, with increased insulin secretion observed in knockout islets.

Conclusions:

• Melatonin synchronizes circadian functions in major organs regulating blood glucose.
• Melatonin negatively regulates insulin secretion.
• Melatonin signaling is crucial for maintaining glucose homeostasis and proper insulin secretion regulation.