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 |
|---|---|
| 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 |
| State | Published - May 10 1994 |
| Externally published | Yes |
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Keywords
- Ca
- insulin
- membrane capacitance
- pancreas
- secretion
ASJC Scopus subject areas
- Genetics
- General
Cite this
Activation of protein kinases and inhibition of protein phosphatases play a central role in the regulation of exocytosis in mouse pancreatic β cells. / Ämmälä, Carina; Eliasson, Lena; Bokvist, Krister; Berggren, Per Olof; Honkanen, Richard E.; Sjöholm, Åke; Rorsman, Patrik.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 10, 10.05.1994, p. 4343-4347.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Activation of protein kinases and inhibition of protein phosphatases play a central role in the regulation of exocytosis in mouse pancreatic β cells
AU - Ämmälä, Carina
AU - Eliasson, Lena
AU - Bokvist, Krister
AU - Berggren, Per Olof
AU - Honkanen, Richard E.
AU - Sjöholm, Åke
AU - Rorsman, Patrik
PY - 1994/5/10
Y1 - 1994/5/10
N2 - 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.
AB - 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.
KW - Ca
KW - insulin
KW - membrane capacitance
KW - pancreas
KW - secretion
UR - http://www.scopus.com/inward/record.url?scp=0028205382&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028205382&partnerID=8YFLogxK
M3 - Article
C2 - 8183910
AN - SCOPUS:0028205382
VL - 91
SP - 4343
EP - 4347
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 10
ER -