The Distinct Role of CBP and p300 in Regulating Hepatic Glucose Production
CBP 和 p300 在调节肝葡萄糖生成中的独特作用
基本信息
- 批准号:8515392
- 负责人:
- 金额:$ 23.21万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-01 至 2016-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcetylationAdultAffectAnimalsAntidiabetic DrugsAwardBindingBloodBlood GlucoseCREB1 geneCell LineCellsComplexCyclic AMPCyclic AMP-Dependent Protein KinasesDataDevelopmentDiabetes MellitusDietDirect CostsEP300 geneEnzyme GeneEnzymesExhibitsFacilities and Administrative CostsFastingFatty acid glycerol estersForskolinGene ExpressionGene Expression ProfileGenesGlucagonGluconeogenesisGlucoseGoalsHealthHepaticHepatocyteHyperglycemiaIndividualInsulinInsulin ResistanceKnockout MiceLiverMediatingMediator of activation proteinMentorsMetforminModalityMorbidity - disease rateMusMutant Strains MiceMutationNewly DiagnosedNon-Insulin-Dependent Diabetes MellitusOkadaic AcidPancreasPatientsPhasePhenotypePhosphorylationPhosphorylation SitePhosphotransferasesPhysiologicalPrevalenceProtein DephosphorylationProtein phosphataseRegulationRelative (related person)RoleSerineSignal PathwaySiteSocietiesTestingTranscriptional RegulationUnited StatesUp-Regulationcalyculin Afeedingglucose productionhepatic gluconeogenesishepatoma cellinsulin signalinglipid biosynthesismortalitymutant mouse modelprogramsreconstitutionsmall hairpin RNA
项目摘要
Diabetes mellitus is becoming more prevalent worldwide, with the number of newly diagnosed adults nearly
tripling between 1980 and 2005 in the US. Fasting hyperglycemia in type 2 diabetes mellitus is caused by
insulin resistance and elevated glucagon levels, which result in non-suppressible hepatic glucose production.
We have shown that both the anti-diabetic agent metformin and insulin phosphorylate the transcriptional co-
activator CBP at serine 436 via PKC¿/¿, leading to the suppression of hepatic glucose production. A related
co-activator, p300, lacking this phosphorylation site, is also am important mediator in regulation glucose
production. We propose 3 aims in this K99/R00 award to further understand transcriptional regulation of
hepatic gluconeogenesis by the p300/CBP class of co-activators. In Aim 1, we will characterize the insulin
signaling and gluconeogenic enzyme gene expression profile in the fasted and fed states in p300 mutant mice
where the PKC¿/¿ phosphorylation site has been reconstituted. In Aim 2, we wil identify the protein
phosphatase mediating glucagon dephosphorylation of CBP at Ser436. In Aim 3, we wil define the role of
each co-activator in the CREB-p300/CBP-TORC2 complex in augmenting gluconeogenesis and the
importance of inter-acetylation of CBP and p300 in mediating hepatic glucose production. The studies in Aim 1
will be finished in mentored K99 phase, while Aims 2 and 3 will be finished in the independent R00 phase. The
mechanistic studies in this proposal, which explore the actions of insulin and glucagon in controlling hepatic
glucose production, will be critical for the development of effective new modalities in the treatment of diabetes
mellitus.
糖尿病在世界范围内变得越来越普遍,新诊断的成年人数量接近
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Ling He', 18)}}的其他基金
Coactivator P300 promotes hepatic steatosis in obesity
共激活剂 P300 促进肥胖患者的肝脂肪变性
- 批准号:
9902424 - 财政年份:2019
- 资助金额:
$ 23.21万 - 项目类别:
Coactivator P300 promotes hepatic steatosis in obesity
共激活剂 P300 促进肥胖患者的肝脂肪变性
- 批准号:
10597095 - 财政年份:2019
- 资助金额:
$ 23.21万 - 项目类别:
Coactivator P300 promotes hepatic steatosis in obesity
共激活剂 P300 促进肥胖患者的肝脂肪变性
- 批准号:
9755549 - 财政年份:2019
- 资助金额:
$ 23.21万 - 项目类别:
Coactivator P300 promotes hepatic steatosis in obesity
共激活剂 P300 促进肥胖患者的肝脂肪变性
- 批准号:
10365981 - 财政年份:2019
- 资助金额:
$ 23.21万 - 项目类别:
Activation of the cAMP-PKA pathway antagonizes metformin action
cAMP-PKA 通路的激活会拮抗二甲双胍的作用
- 批准号:
9186543 - 财政年份:2015
- 资助金额:
$ 23.21万 - 项目类别:
Activation of the cAMP-PKA pathway antagonizes metformin action
cAMP-PKA 通路的激活会拮抗二甲双胍的作用
- 批准号:
9008164 - 财政年份:2015
- 资助金额:
$ 23.21万 - 项目类别:
The Distinct Role of CBP and p300 in Regulating Hepatic Glucose Production
CBP 和 p300 在调节肝葡萄糖生成中的独特作用
- 批准号:
8310339 - 财政年份:2011
- 资助金额:
$ 23.21万 - 项目类别:
The Distinct Role of CBP and p300 in Regulating Hepatic Glucose Production
CBP 和 p300 在调节肝葡萄糖生成中的独特作用
- 批准号:
8328726 - 财政年份:2011
- 资助金额:
$ 23.21万 - 项目类别:
The Distinct Role of CBP and p300 in Regulating Hepatic Glucose Production
CBP 和 p300 在调节肝葡萄糖生成中的独特作用
- 批准号:
7989326 - 财政年份:2010
- 资助金额:
$ 23.21万 - 项目类别:
The Distinct Role of CBP and p300 in Regulating Hepatic Glucose Production
CBP 和 p300 在调节肝葡萄糖生成中的独特作用
- 批准号:
8115793 - 财政年份:2010
- 资助金额:
$ 23.21万 - 项目类别:
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