Activation of insulin and IGF-1 signaling pathways by melatonin through MT1 receptor in isolated rat pancreatic islets.
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.
Picinato
M C
MC
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Hirata
A E
AE
Cipolla-Neto
J
J
Curi
R
R
Carvalho
C R O
CR
Anhê
G F
GF
Carpinelli
A R
AR
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D000078790:Insulin Secretion; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008550:Melatonin / Q000378:metabolism*; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D044122:Receptor, Melatonin, MT1; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat; D008550:Melatonin