PMID- 21424898
OWN - NLM
STAT- MEDLINE
DCOM- 20111004
LR  - 20211020
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 54
IP  - 7
DP  - 2011 Jul
TI  - Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like 
      peptide-1 secretion in mice.
PG  - 1824-30
LID - 10.1007/s00125-011-2119-3 [doi]
AB  - AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1), a hormone with potent 
      antihyperglycaemic effects, is produced and secreted from highly specialised gut 
      endocrine L-cells. It regulates glucose homeostasis by promoting 
      glucose-dependent insulin secretion, suppressing glucagon secretion and enhancing 
      insulin sensitivity. Similar to islet alpha and beta cells, L-cells are 
      electrically excitable, and express calcium channels and ATP-sensitive potassium 
      channels. GLP-1 is also stored in secretory granules, the exocytosis of which is 
      triggered by increased intracellular calcium levels. Although the calcium 
      dependence of GLP-1 granule exocytosis is well established, the identities of 
      calcium-sensing proteins in GLP-1 secretion remain elusive. Here we tested 
      whether synaptotagmin-7, a calcium sensor in pancreatic alpha and beta cells, 
      regulates GLP-1 secretion. METHODS: We studied GLP-1 secretion using 
      synaptotagmin-7 knockout (KO) mice and GLUTag cells with lentiviral-mediated 
      synaptotagmin-7 silencing. RESULTS: We found that synaptotagmin-7 was 
      co-localised with GLP-1 in intestinal L-cells. GLP-1 secretion was impaired in 
      synaptotagmin-7 KO mice when they were challenged by glucose ingestion. 
      Lentiviral knockdown (KD) of synaptotagmin-7 in GLUTag cells led to similar 
      reductions in GLP-1 secretion, as determined by biochemical assays and by 
      membrane capacitance measurements. Calcium response was not altered in 
      synaptotagmin-7 KD cells. CONCLUSIONS/INTERPRETATION: These results demonstrate 
      that synaptotagmin-7 functions as a positive regulator of GLP-1 secretion in 
      intestinal L-cells and GLUTag cells, consistent with its proposed role as a 
      calcium sensor in GLP-1 secretion.
FAU - Gustavsson, N
AU  - Gustavsson N
AD  - Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for 
      Science, Technology and Research (A STAR), 02-02 Helios, 11 Biopolis Way, 
      Singapore, 138667, Republic of Singapore.
FAU - Wang, Y
AU  - Wang Y
FAU - Kang, Y
AU  - Kang Y
FAU - Seah, T
AU  - Seah T
FAU - Chua, S
AU  - Chua S
FAU - Radda, G K
AU  - Radda GK
FAU - Han, W
AU  - Han W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110322
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (RNA, Small Interfering)
RN  - 134193-27-4 (Synaptotagmins)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Electrophysiology
MH  - Glucagon-Like Peptide 1/*metabolism
MH  - Immunohistochemistry
MH  - Intestines/*cytology
MH  - Mice
MH  - Mice, Knockout
MH  - Polymerase Chain Reaction
MH  - RNA, Small Interfering/genetics
MH  - Synaptotagmins/genetics/*metabolism
EDAT- 2011/03/23 06:00
MHDA- 2011/10/05 06:00
CRDT- 2011/03/23 06:00
PHST- 2011/01/03 00:00 [received]
PHST- 2011/02/22 00:00 [accepted]
PHST- 2011/03/23 06:00 [entrez]
PHST- 2011/03/23 06:00 [pubmed]
PHST- 2011/10/05 06:00 [medline]
AID - 10.1007/s00125-011-2119-3 [doi]
PST - ppublish
SO  - Diabetologia. 2011 Jul;54(7):1824-30. doi: 10.1007/s00125-011-2119-3. Epub 2011 
      Mar 22.