Abstract:
:Cyclic AMP (cAMP) and Ca(2+) are key regulators of exocytosis in many cells, including insulin-secreting beta cells. Glucose-stimulated insulin secretion from beta cells is pulsatile and involves oscillations of the cytoplasmic Ca(2+) concentration ([Ca(2+)](i)), but little is known about the detailed kinetics of cAMP signaling. Using evanescent-wave fluorescence imaging we found that glucose induces pronounced oscillations of cAMP in the submembrane space of single MIN6 cells and primary mouse beta cells. These oscillations were preceded and enhanced by elevations of [Ca(2+)](i). However, conditions raising cytoplasmic ATP could trigger cAMP elevations without accompanying [Ca(2+)](i) rise, indicating that adenylyl cyclase activity may be controlled also by the substrate concentration. The cAMP oscillations correlated with pulsatile insulin release. Whereas elevation of cAMP enhanced secretion, inhibition of adenylyl cyclases suppressed both cAMP oscillations and pulsatile insulin release. We conclude that cell metabolism directly controls cAMP and that glucose-induced cAMP oscillations regulate the magnitude and kinetics of insulin exocytosis.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Dyachok O,Idevall-Hagren O,Sågetorp J,Tian G,Wuttke A,Arrieumerlou C,Akusjärvi G,Gylfe E,Tengholm Adoi
10.1016/j.cmet.2008.06.003subject
Has Abstractpub_date
2008-07-01 00:00:00pages
26-37issue
1eissn
1550-4131issn
1932-7420pii
S1550-4131(08)00174-5journal_volume
8pub_type
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