PMID- 27207520
OWN - NLM
STAT- MEDLINE
DCOM- 20170605
LR  - 20181113
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 65
IP  - 7
DP  - 2016 Jul
TI  - Synaptotagmin-7 Functions to Replenish Insulin Granules for Exocytosis in Human 
      Islet beta-Cells.
PG  - 1962-76
LID - 10.2337/db15-1436 [doi]
AB  - Synaptotagmin (Syt)-7, a major component of the exocytotic machinery in neurons, 
      is also the major Syt in rodent pancreatic beta-cells shown to mediate 
      glucose-stimulated insulin secretion (GSIS). However, Syt-7's precise exocytotic 
      actions in beta-cells remain unknown. We show that Syt-7 is abundant in human 
      beta-cells. Adenovirus-short hairpin RNA knockdown (KD) of Syt-7 in human islets 
      reduced first- and second-phase GSIS attributed to the reduction of exocytosis of 
      predocked and newcomer insulin secretory granules (SGs). Glucose stimulation 
      expectedly induced Syt-7 association in a Ca(2+)-dependent manner with syntaxin-3 
      and syntaxin-1A soluble N-ethylmaleimide-sensitive factor attachment protein 
      receptor (SNARE) complexes known to mediate exocytosis of newcomer and predocked 
      SGs, respectively. However, Syt-7-KD did not disrupt SNARE complex assembly. 
      Instead, electron microscopy analysis showed that Syt-7-KD reduced the 
      recruitment of SGs to the plasma membrane after glucose-stimulated depletion, 
      which could not be rescued by glucagon-like peptide 1 pretreatment. To assess the 
      possibility that this new action of Syt-7 on SG recruitment may involve 
      calmodulin (CaM), pretreatment of islets with CaM blocker calmidazolium showed 
      effects very similar to those of Syt-7-KD. Syt-7 therefore plays a novel more 
      dominant function in the replenishment of releasable SG pools in human beta-cells 
      than its previously purported role in exocytotic fusion per se.
CI  - (c) 2016 by the American Diabetes Association. Readers may use this article as long 
      as the work is properly cited, the use is educational and not for profit, and the 
      work is not altered.
FAU - Dolai, Subhankar
AU  - Dolai S
AD  - Department of Medicine, University of Toronto, Toronto, ON, Canada.
FAU - Xie, Li
AU  - Xie L
AD  - Department of Medicine, University of Toronto, Toronto, ON, Canada.
FAU - Zhu, Dan
AU  - Zhu D
AD  - Department of Medicine, University of Toronto, Toronto, ON, Canada.
FAU - Liang, Tao
AU  - Liang T
AD  - Department of Medicine, University of Toronto, Toronto, ON, Canada.
FAU - Qin, Tairan
AU  - Qin T
AD  - Department of Medicine, University of Toronto, Toronto, ON, Canada.
FAU - Xie, Huanli
AU  - Xie H
AD  - Department of Medicine, University of Toronto, Toronto, ON, Canada.
FAU - Kang, Youhou
AU  - Kang Y
AD  - Department of Medicine, University of Toronto, Toronto, ON, Canada.
FAU - Chapman, Edwin R
AU  - Chapman ER
AD  - Department of Neuroscience, Howard Hughes Medical Institute, University of 
      Wisconsin-Madison, Madison, WI.
FAU - Gaisano, Herbert Y
AU  - Gaisano HY
AD  - Department of Medicine, University of Toronto, Toronto, ON, Canada Department of 
      Physiology, University of Toronto, Toronto, ON, Canada 
      herbert.gaisano@utoronto.ca.
LA  - eng
GR  - R01 MH061876/MH/NIMH NIH HHS/United States
GR  - R01 NS072905/NS/NINDS NIH HHS/United States
GR  - MOP86544/CIHR/Canada
GR  - MOP89889/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160426
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Imidazoles)
RN  - 0 (Insulin)
RN  - 0 (Qa-SNARE Proteins)
RN  - 0 (SNARE Proteins)
RN  - 134193-27-4 (Synaptotagmins)
RN  - 4R9H38JAWL (calmidazolium)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - IY9XDZ35W2 (Glucose)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Calcium/metabolism
MH  - Exocytosis/drug effects/*physiology
MH  - Female
MH  - Glucagon-Like Peptide 1/pharmacology
MH  - Glucose/pharmacology
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Insulin/*metabolism
MH  - Insulin-Secreting Cells/drug effects/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Qa-SNARE Proteins/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - SNARE Proteins/metabolism
MH  - Secretory Vesicles/*metabolism
MH  - Synaptotagmins/*metabolism
PMC - PMC5384637
EDAT- 2016/05/22 06:00
MHDA- 2017/06/06 06:00
PMCR- 2017/07/01
CRDT- 2016/05/22 06:00
PHST- 2015/10/19 00:00 [received]
PHST- 2016/04/16 00:00 [accepted]
PHST- 2016/05/22 06:00 [entrez]
PHST- 2016/05/22 06:00 [pubmed]
PHST- 2017/06/06 06:00 [medline]
PHST- 2017/07/01 00:00 [pmc-release]
AID - db15-1436 [pii]
AID - 1436 [pii]
AID - 10.2337/db15-1436 [doi]
PST - ppublish
SO  - Diabetes. 2016 Jul;65(7):1962-76. doi: 10.2337/db15-1436. Epub 2016 Apr 26.