Abstract:
:The mechanisms that regulate insulin secretion were investigated using capacitance measurements of exocytosis in single beta cells maintained in tissue culture. Exocytosis was stimulated by voltage-clamp depolarizations to activate the voltage-dependent Ca2+ channels that mediate Ca2+ influx into the beta cell. Under basal conditions, the exocytotic responses were small despite large Ca2+ currents. The exocytotic responses were dramatically increased (10- to 20-fold) by conditions that promote protein phosphorylation, such as activation of protein kinases A and C or inhibition of protein phosphatases. The stimulation of secretion was not due to an enhancement of Ca2+ influx and both peak and integrated Ca2+ currents were largely unaffected. Our data indicate that exocytosis in the insulin-secreting pancreatic beta cell is determined by a balance between protein phosphorylation and dephosphorylation. They further suggest that although Ca2+ is required for the initiation of exocytosis, modulation of exocytosis by protein kinases and phosphatases, at a step distal to the elevation of Ca2+, is of much greater quantitative importance. Thus an elevation of Ca2+ may represent a permissive rather than a decisive factor in the regulation of the insulin secretory process.
journal_name
Proc Natl Acad Sci U S Aauthors
Ammälä C,Eliasson L,Bokvist K,Berggren PO,Honkanen RE,Sjöholm A,Rorsman Pdoi
10.1073/pnas.91.10.4343subject
Has Abstractpub_date
1994-05-10 00:00:00pages
4343-7issue
10eissn
0027-8424issn
1091-6490journal_volume
91pub_type
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