In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat hypothalamus
Version of Record online: 16 JUN 2004
Journal of Neurochemistry
Volume 90, Issue 3, pages 559–566, August 2004
How to Cite
Anhê, G. F., Caperuto, L. C., Pereira-Da-Silva, M., Souza, L. C., Hirata, A. E., Velloso, L. A., Cipolla-Neto, J. and Carvalho, C. R. O. (2004), In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat hypothalamus. Journal of Neurochemistry, 90: 559–566. doi: 10.1111/j.1471-4159.2004.02514.x
- Issue online: 18 JUN 2004
- Version of Record online: 16 JUN 2004
- Received December 8, 2003; revised manuscript received March 4, 2004; accepted March 5, 2004.
- insulin receptor;
- tyrosine phosphorylation
Melatonin is the pineal hormone that acts via a pertussis toxin-sensitive G-protein to inhibit adenylate cyclase. However, the intracellular signalling effects of melatonin are not completely understood. Melatonin receptors are mainly present in the suprachiasmatic nucleus (SCN) and pars tuberalis of both humans and rats. The SCN directly controls, amongst other mechanisms, the circadian rhythm of plasma glucose concentration. In this study, using immunoprecipitation and immunoblotting, we show that melatonin induces rapid tyrosine phosphorylation and activation of the insulin receptor β-subunit tyrosine kinase (IR) in the rat hypothalamic suprachiasmatic region. Upon IR activation, tyrosine phosphorylation of IRS-1 was detected. In addition, melatonin induced IRS-1/PI(3)-kinase and IRS-1/SHP-2 associations and downstream AKT serine phosphorylation and MAPK (mitogen-activated protein kinase) phosphorylation, respectively. These results not only indicate a new signal transduction pathway for melatonin, but also a potential cross-talk between melatonin and insulin.