http://www.nature.com/nature/journal/v439/n7074/full/nature04410.html
cAMP ( syklinenAMP) on yleinen toisiolähetti useissa solupintareseptoreissa, joiden kautta säätyy erilaisia solutapahtumia, sekreetiota, aineenvaihduntaa, geenintranskriptiota.
Haimasaarekkeen beeta-solussa cAMP vahvsitaa jonisoidusta kalsiumista riippuvaa exosytoosia ja se välittää sitä insuliininvapautumisen stimulaatiota, joka tulee hormoneista glukagoni ja GLIP-1 (glukagonin kaltaisesta peptidistä)
- Cyclic AMP is a ubiquitous second messenger that transduces signals from a variety of cell surface receptors to regulate diverse cellular functions, including secretion, metabolism and gene transcription. In pancreatic β-cells, cAMP potentiates Ca2+-dependent exocytosis1, 2, 3 and mediates the stimulation of insulin release exerted by the hormones glucagon and glucagon-like peptide-1 (GLP-1) (refs 4, 5–6).
- Whereas Ca2+ signals have been extensively characterized and shown to involve oscillations important for the temporal control of insulin secretion4, 7, 8, the kinetics of receptor-triggered cAMP signals is unknown.
- Here we introduce a new ratiometric evanescent-wave-microscopy approach to measure cAMP concentration beneath the plasma membrane, and show that insulin-secreting β-cells respond to glucagon and GLP-1 with marked cAMP oscillations.
- Simultaneous measurements of intracellular Ca2+ concentration revealed that the two messengers are interlinked and reinforce each other.
- Moreover, cAMP oscillations are capable of inducing rapid on–off Ca2+ responses, but only sustained elevation of cAMP concentration induces nuclear translocation of the catalytic subunit of the cAMP-dependent protein kinase.
- Our results establish a new signalling mode for cAMP and indicate that temporal encoding of cAMP signals might constitute a basis for differential regulation of downstream cellular targets.
Inga kommentarer:
Skicka en kommentar