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Activation of insulin and IGF‐1 signaling pathways by melatonin through MT1 receptor in isolated rat pancreatic islets

2007; Wiley; Volume: 44; Issue: 1 Linguagem: Inglês

10.1111/j.1600-079x.2007.00493.x

1600-079X

Maria Cristina Picinato Medeiros de Araújo, Aparecida Emiko Hirata, José Cipolla‐Neto, Rui Curi, Carla Roberta de Oliveira Carvalho, Gabriel Forato Anhê, Ângelo Rafael Carpinelli,

Circadian rhythm and melatonin

Abstract: Melatonin diminishes insulin release through the activation of MT1 receptors and a reduction in cAMP production in isolated pancreatic islets of neonate and adult rats and in INS‐1 cells (an insulin‐secreting cell line). The pancreas of pinealectomized rats exhibits degenerative pathological changes with low islet density, indicating that melatonin plays a role to ensure the functioning of pancreatic beta cells. By using immunoprecipitation and immunoblotting analysis we demonstrated, in isolated rat pancreatic islets, that melatonin induces insulin growth factor receptor (IGF‐R) and insulin receptor (IR) tyrosine phosphorylation and mediates the activities of the PI3K/AKT and MEK/ERKs pathways, which are involved in cell survival and growth, respectively. Thus, the effects of melatonin on pancreatic islets do not involve a reduction in cAMP levels only. This indoleamine may regulate growth and differentiation of pancreatic islets by activating IGF‐I and insulin receptor signaling pathways.