Calcium regulation of glucagon-like peptide-1 secretion.
Glucagon-like peptide (GLP-1), a hormone secreted from enteroendocrine L-cells in response to nutrient ingestion. Because of its strong potentiating effect on insulin release, GLP-1 now becomes a basis for new class diabetes treatment strategies. However, molecular mechanism of GLP-1 secretion re...
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Format: | Final Year Project |
Language: | English |
Published: |
2010
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Online Access: | http://hdl.handle.net/10356/39459 |
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Institution: | Nanyang Technological University |
Language: | English |
Summary: | Glucagon-like peptide (GLP-1), a hormone secreted from enteroendocrine L-cells in
response to nutrient ingestion. Because of its strong potentiating effect on insulin
release, GLP-1 now becomes a basis for new class diabetes treatment strategies.
However, molecular mechanism of GLP-1 secretion regulation has remained elusive.
It is known that GLP-1 secretion is calcium (Ca2+) -dependent but extent of Ca2+
regulation is not established. The aim of this study was to examine the relation
between Ca2+ response and GLP-1 secretion and search for the proteins serving as
Ca2+ sensors. In β-cells, the identities of Ca2+ sensors only recently started to
emerge. Here we tested whether synaptotagmin-2 (Syt2) operates Ca2+ sensing in
GLP-1 release by generating Syt2 knockdown (KD) GLUTag cells. We characterized
dose-dependence for Ca2+ response to stimulus. For glucose stimulation, GLP-1
secretion reflected the amplitude of Ca2+ increase. In contrast, glutamine had a
strong non- Ca2+ dependent component in addition to its Ca2+ -dependent release.
Syt2 KD resulted in a reduction of GLP-1 release, however the subcellular
localization showed very little co-localization with GLP-1 containing granules.
Therefore, Syt2 may directly operate Ca2+ sensing of readily releasable pool of GLP-
1 granules and may also regulate GLP-1 secretion indirectly through regulation of
granule trafficking. |
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