Research Project
Grant-in-Aid for Scientific Research (C)
The mechanism of glucose-induced biphasic insulin release is unknown. We used total internal reflection fluorescence (TIRF) imaging analysis to reveal the process of first- and second-phase insulin exocytosis in pancreatic 13 cells. This analysis showed that previously docked insulin granules fused at the. site of syntaxin (Synt) 1A clusters during the first phase; however, the newcomers fused during the second phase external to the Synt1A clusters. In order to reveal the function of Synt1A in phasic insulin exocytosis, we generated Synt1A-knockout (Synt1A^<-/->) mice. Synt1A^<-/->β cells showed fewer previously docked granules with no fusion during the first phase; second-phase fusion from newcomers was well preserved. Rescue experiments using adenovirus-expressed Synt1A in Synt1A^<-/->β cells showed restoration of granule docking status and fusion events during the first phase. Inhibition of the functions of other plasma membrane syntaxins, Synt3 and Synt4, did not affect second-phase insulin exocytosis by experiments with dominant negative forms of Synt3 and Synt4. Thus, our findings show that the first phase is Synt1A-dependent, but the second phase is not. This indicates that insulin exocytosis underlying biphasic release differs spatially and mechanistically.
All 2008 2007 2006 2005
All Journal Article (45 results) (of which Peer Reviewed: 17 results) Presentation (21 results) Book (4 results)
Diabetologia 51
Pages: 827-835
Biochem.J. 412
Pages: 93-101
Biochem. J 412
Glycobiology 17
Pages: 127-140
Cell 129
Pages: 359-370
J Cell Biol 177
Pages: 695-705
J Biol Chem 282
Pages: 2707-2716
Science 318
Pages: 1249-1250
Methods Mol.Biol 440
Pages: 259-268
Jan 26 282 (4)
Methods Mol. Biol 440
Science. 318
Methods Mol. Biol. 440
内分泌・糖尿病科 24
Pages: 69-75
内分泌・糖尿病科 25
Pages: 265-272
J Biol Chem. 282
Pages: 2707-16
Pages: 127-40
J. Cell. Biol. In press
Diabetes 55
Pages: 2819-2825
Proc.SPIE 6088
Pages: 449-454
Proc. SPIE 6088
J Biochem (Tokyo). 140
Pages: 1-5
10018843301
Pages: 2819-25
Mol Biol Cell 16
Pages: 3289-3300
J Clin Invest 115
Pages: 388-396
FEBS Lett 579
Pages: 1602-1606
Hypertension 45
Pages: 1188-1193
Mol. Biol. Cell 16
日本薬理学雑誌 126
Pages: 399-405
10018621698
Am J Physiol Endocrinol Metab. 289