Diabetes 53:S59-S62, 2004
© 2004 by the American Diabetes Association, Inc.
Section II: Beta-Cell Therapeutic Targets Other Than ATP-Sensitive K+ Channels |
Integration of ATP, cAMP, and Ca2+ Signals in Insulin Granule Exocytosis
Tadao Shibasaki,
Yasuhiro Sunaga, and
Susumu Seino
Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
Intracellular ATP, cAMP, and Ca2+ are major signals involved in the regulation of insulin secretion in the pancreatic ß-cell. We recently found that the ATP-sensitive K+ channel (KATP channel) as an ATP sensor, cAMP-GEFII as a cAMP sensor, Piccolo as a Ca2+ sensor, and L-type voltage-dependent Ca2+ channel (VDCC) can interact with each other. In the present study, we examined the effects of cAMP and ATP on the interaction of cAMP-GEFII and sulfonylurea receptor-1 (SUR1). Interaction of cAMP-GEFII with SUR1 was inhibited by the cAMP analog 8-bromo-cAMP but not by ATP, and the inhibition by 8-bromo-cAMP persisted in the presence of ATP. In addition, SUR1, cAMP-GEFII, and Piccolo could form a complex. Piccolo also interacted with the 11.2 subunit of VDCC in a Ca2+-independent manner. These data suggest that the interactions of the KATP channel, cAMP-GEFII, Piccolo, and L-type VDCC are regulated by intracellular signals such as cAMP and Ca2+ and that the ATP, cAMP, and Ca2+ signals are integrated at a specialized region of pancreatic ß-cells.
Address correspondence and reprint requests to S. Seino, Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017. E-mail: seino{at}med.kobe-u.ac.jp

CiteULike Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
G. G. Holz, G. Kang, M. Harbeck, M. W. Roe, and O. G. Chepurny
Cell physiology of cAMP sensor Epac
J. Physiol.,
November 15, 2006;
577(1):
5 - 15.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Kang, O. G. Chepurny, B. Malester, M. J. Rindler, H. Rehmann, J. L. Bos, F. Schwede, W. A. Coetzee, and G. G. Holz
cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic {beta} cells and rat INS-1 cells
J. Physiol.,
June 15, 2006;
573(3):
595 - 609.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Q. Du, S. Jovanovic, A. Clelland, A. Sukhodub, G. Budas, K. Phelan, V. Murray-Tait, L. Malone, and A. Jovanovic
Overexpression of SUR2A generates a cardiac phenotype resistant to ischemia
FASEB J,
June 1, 2006;
20(8):
1131 - 1141.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Hambrock, C. B. de Oliveira Franz, S. Hiller, and H. Osswald
Glibenclamide-Induced Apoptosis Is Specifically Enhanced by Expression of the Sulfonylurea Receptor Isoform SUR1 but Not by Expression of SUR2B or the Mutant SUR1(M1289T)
J. Pharmacol. Exp. Ther.,
March 1, 2006;
316(3):
1031 - 1037.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Seino and T. Shibasaki
PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis
Physiol Rev,
October 1, 2005;
85(4):
1303 - 1342.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2004 by the American Diabetes Association.
|
|
| |
|