GLUCOKINASE GENE EXPRESSION IN THE PANCREATIC BETA CELL
GLUCOKINASE GENE EXPRESSION IN THE PANCREATIC BETA CELL
批准号:
3243754
负责人:
MARK A MAGNUSON
金额:
$11.78万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1990
资助国家:
美国
项目状态:
已结题
起止时间:
1990-06-01 至 1995-05-31
关键词:
DNA footprinting antisense nucleic acid enzyme mechanism enzyme structure fusion gene gene deletion mutation gene expression genetic promoter element glucokinase glucose metabolism molecular cloning neoplastic cell culture for noncancer research pancreatic islet function polymerase chain reaction protein purification protein structure function transcription factor transfection transposon /insertion element
中文摘要
胰腺细胞的电、离子和分泌反应
英文摘要
The electrical, ionic, and secretory responses of pancreatic beta cells to
glucose are mediated by the metabolism of the sugar. Glucokinase (GK)
catalyzes the initial and rate limiting step in the utilization of glucose
by the beta cell at physiologic glucose concentrations and is thought to
play an important role in modulating insulin secretion. To study the
function and regulation of GK in the beta cell further, we have
characterized cDNAs encoding GK from both the liver and insulinoma tissue
and have mapped the mapped the transcription units in both tissues. Our
studies have shown there are two different promoters in a single GK gene.
One promoter is expressed specifically in the liver and appears to be
regulated by insulin while another promoter, located further upstream,
appears active only in the beta cell. We are proposing to study the
function and regulation of GK in insulinoma cell lines (Aim 1) and to
examine the GK beta cell promoter using a fusion gene analysis (Aim 2). In
Aim 1 complimentary approaches will be used to test the function of GK as
the beta cell "glucose sensor". By altering the expression of GK in two
different insulinoma cell lines we hope to alter the "set point" of
glucose-stimulated insulin secretion. RINm5F cells have normal glucose
uptake but appear to lack a high-Km glucose phosphorylating activity and do
not secrete insulin in response to glucose. Another cell line, beta-TC,
shows high-Km glucose usage but is stimulated to secrete insulin by less
than normal glucose concentrations. We will determine the effects of
expressing GK in the RINm5f cells and the effects of expressing GK
antisense RNA in the beta-TC cells. In Aim 2 an analysis of the beta cell
GK promoter will be undertaken using a fusion gene approach. Both a 5'
deletional analysis and the use of internal deletion mutants should enable
us to identify elements necessary for the beta cell-specific expression of
GK. Elements important for the cell type expression of GK are likely to
bind factors which are important for beta cell-specific gene expression.
These factors will be studied further using mobility shift and methylation
interference assays. Efforts to purify and clone one of these factors will
be initiated.
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Coordinating Center for Beta Cell Biology Consortium
-
批准号:8121183
-
项目类别:
-
资助金额:$11.51万
-
财政年份:2010
-
负责人:MARK A MAGNUSON
-
依托单位:
Transgenic Mouse
-
批准号:8180600
-
项目类别:
-
资助金额:$9.44万
-
财政年份:2010
-
负责人:MARK A MAGNUSON
-
依托单位:
Genetic control of pancreatic endocrine cell development
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批准号:7993178
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项目类别:
-
资助金额:$133.62万
-
财政年份:2010
-
负责人:MARK A MAGNUSON
-
依托单位:
Genetic control of pancreatic endocrine cell development
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批准号:8717642
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项目类别:
-
资助金额:$10.0万
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财政年份:2010
-
负责人:MARK A MAGNUSON
-
依托单位:
Genetic control of pancreatic endocrine cell development
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批准号:8522192
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项目类别:
-
资助金额:$124.36万
-
财政年份:2010
-
负责人:MARK A MAGNUSON
-
依托单位:
Genetic control of pancreatic endocrine cell development
-
批准号:8144905
-
项目类别:
-
资助金额:$129.87万
-
财政年份:2010
-
负责人:MARK A MAGNUSON
-
依托单位:
Genetic control of pancreatic endocrine cell development
-
批准号:8316316
-
项目类别:
-
资助金额:$129.87万
-
财政年份:2010
-
负责人:MARK A MAGNUSON
-
依托单位:
Coordinating Center for Beta Cell Biology Consortium
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批准号:8010566
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项目类别:
-
资助金额:$12.96万
-
财政年份:2010
-
负责人:MARK A MAGNUSON
-
依托单位:
Coordinating Center for Beta Cell Biology Consortium
-
批准号:7825081
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项目类别:
-
资助金额:$259.59万
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财政年份:2009
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负责人:MARK A MAGNUSON
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依托单位:
EFFECTS OF LIVER SPECIFIC KNOCKOUT OF PEPCK ON GLUCOSE METABOLISM
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批准号:7724113
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项目类别:
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资助金额:$1.05万
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财政年份:2008
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负责人:MARK A MAGNUSON
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依托单位:
EFFECTS OF LIVER SPECIFIC KNOCKOUT OF PEPCK ON GLUCOSE METABOLISM
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批准号:7600847
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项目类别:
-
资助金额:$1.51万
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财政年份:2007
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负责人:MARK A MAGNUSON
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依托单位:
EFFECTS OF LIVER SPECIFIC KNOCKOUT OF PEPCK ON GLUCOSE METABOLISM
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批准号:7357890
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项目类别:
-
资助金额:$1.17万
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财政年份:2006
-
负责人:MARK A MAGNUSON
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依托单位:
EFFECTS OF LIVER SPECIFIC KNOCKOUT OF PEPCK ON GLUCOSE METABOLISM
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批准号:7180729
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项目类别:
-
资助金额:$2.1万
-
财政年份:2005
-
负责人:MARK A MAGNUSON
-
依托单位:
Coordinating Center for Beta Cell Biology Consortium
-
批准号:8525392
-
项目类别:
-
资助金额:$357.0万
-
财政年份:2005
-
负责人:MARK A MAGNUSON
-
依托单位:
Coordinating Center for Beta Cell Biology Consortium
-
批准号:8326734
-
项目类别:
-
资助金额:$370.0万
-
财政年份:2005
-
负责人:MARK A MAGNUSON
-
依托单位:
Coordinating Center for Beta Cell Biology Consortium
-
批准号:7684082
-
项目类别:
-
资助金额:$342.06万
-
财政年份:2005
-
负责人:MARK A MAGNUSON
-
依托单位:
Coordinating Center for Beta Cell Biology Consortium
-
批准号:7913613
-
项目类别:
-
资助金额:$523.91万
-
财政年份:2005
-
负责人:MARK A MAGNUSON
-
依托单位:
Endocrine cell induction during pancreas
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批准号:7056487
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项目类别:
-
资助金额:$36.46万
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财政年份:2005
-
负责人:MARK A MAGNUSON
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依托单位:
Administrative Core
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批准号:7056498
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项目类别:
-
资助金额:$7.6万
-
财政年份:2005
-
负责人:MARK A MAGNUSON
-
依托单位:
Coordinating Center for Beta Cell Biology Consortium
-
批准号:7500228
-
项目类别:
-
资助金额:$43.23万
-
财政年份:2005
-
负责人:MARK A MAGNUSON
-
依托单位:
海外基金