Abstract
The mechanisms that regulate insulin secretion were investigated using capacitance measurements of exocytosis in single β 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 β 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 β 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.
Original language | English (US) |
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Pages (from-to) | 4343-4347 |
Number of pages | 5 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 91 |
Issue number | 10 |
DOIs | |
State | Published - May 10 1994 |
Externally published | Yes |
Keywords
- Ca
- insulin
- membrane capacitance
- pancreas
- secretion
ASJC Scopus subject areas
- Genetics
- General