Melatonin signalling and islet function
Claire Lyons, Clinical Research Centre, Malmö, Sweden
Melatonin, a hormone mediating sleep and wake cycles, is associated with dysregulated metabolism. Two receptors mediate melatonin signaling MTNR1A and MTNR1B (Mt1 and Mt2 in rodents), which are distributed in several tissues including the insulin producing β-cells and glucagon producing ∝-cells of the pancreas. Work from our group established that a genetic variant, a single nucleotide polymorphism (SNP) mapping to the MTNR1B locus, increases the risk of developing Type 2 Diabetes (T2D), by increased MTNR1B expression on β-cells and inhibition of insulin secretion.
Far less is known about the MTNR1A receptor (Mt1), present mainly on ∝-cells. Thus, this forms the overall aim of the present application; to map the role of Mt1 signaling in ∝-cells. We can demonstrate that mice lacking the Mt1 receptor (Mt1-/-) display hyperglucagonemia, both in vivo and at the islet level. However, the mechanistic pathways leading to this is yet to be determined.
Therefore, the specific aims are as follows:
- Aim 1: Investigate if loss of Mt1 causes changes in ∝-cell plasma membrane potential to induce hyperglucagonemia
- Aim 2: Determine if melatonin signaling in ∝-cells is acting through Gq or Gi pathways in mouse islets
Grant awarded: €4,250