Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice

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Standard

Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice. / Gustavsson, N; Wang, Y; Kang, Y; Seah, T; Chua, S; Radda, G K; Han, W.

In: Diabetologia, Vol. 54, No. 7, 07.2011, p. 1824-30.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Gustavsson, N, Wang, Y, Kang, Y, Seah, T, Chua, S, Radda, GK & Han, W 2011, 'Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice', Diabetologia, vol. 54, no. 7, pp. 1824-30. https://doi.org/10.1007/s00125-011-2119-3

APA

Gustavsson, N., Wang, Y., Kang, Y., Seah, T., Chua, S., Radda, G. K., & Han, W. (2011). Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice. Diabetologia, 54(7), 1824-30. https://doi.org/10.1007/s00125-011-2119-3

Vancouver

Gustavsson N, Wang Y, Kang Y, Seah T, Chua S, Radda GK et al. Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice. Diabetologia. 2011 Jul;54(7):1824-30. https://doi.org/10.1007/s00125-011-2119-3

Author

Gustavsson, N ; Wang, Y ; Kang, Y ; Seah, T ; Chua, S ; Radda, G K ; Han, W. / Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice. In: Diabetologia. 2011 ; Vol. 54, No. 7. pp. 1824-30.

Bibtex

@article{85054d66c0584014b7c3569e34a0ecfa,
title = "Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice",
abstract = "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.",
keywords = "Animals, Blotting, Western, Cells, Cultured, Electrophysiology, Glucagon-Like Peptide 1, Immunohistochemistry, Intestines, Mice, Mice, Knockout, Polymerase Chain Reaction, RNA, Small Interfering, Synaptotagmins, Journal Article, Research Support, Non-U.S. Gov't",
author = "N Gustavsson and Y Wang and Y Kang and T Seah and S Chua and Radda, {G K} and W Han",
year = "2011",
month = jul,
doi = "10.1007/s00125-011-2119-3",
language = "English",
volume = "54",
pages = "1824--30",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",
number = "7",

}

RIS

TY - JOUR

T1 - Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice

AU - Gustavsson, N

AU - Wang, Y

AU - Kang, Y

AU - Seah, T

AU - Chua, S

AU - Radda, G K

AU - Han, W

PY - 2011/7

Y1 - 2011/7

N2 - 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.

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.

KW - Animals

KW - Blotting, Western

KW - Cells, Cultured

KW - Electrophysiology

KW - Glucagon-Like Peptide 1

KW - Immunohistochemistry

KW - Intestines

KW - Mice

KW - Mice, Knockout

KW - Polymerase Chain Reaction

KW - RNA, Small Interfering

KW - Synaptotagmins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1007/s00125-011-2119-3

DO - 10.1007/s00125-011-2119-3

M3 - Journal article

C2 - 21424898

VL - 54

SP - 1824

EP - 1830

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 7

ER -

ID: 172513150