Physiological and functional effects of beta-cell-specific inactivation of the PGE2 receptor EP3
Physiological and functional effects of beta-cell-specific inactivation of the PGE2 receptor EP3
PGE2 受体 EP3 β 细胞特异性失活的生理和功能影响
批准号：
10248348
负责人：
Ashley A Christensen
金额：
$1.15万
依托单位：
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
项目状态：
已结题
起止时间：
2020-09-01 至 2021-12-31
关键词：
AblationAdenylate CyclaseAdipose tissueAdultAffectAgeAmericanB Cell ProliferationBeta CellBindingBrainCell ProliferationCell SurvivalCell physiologyCessation of lifeCouplesCyclic AMP-Dependent Protein KinasesDataDiabetes MellitusDietDinoprostoneFOXM1 geneFailureFatty acid glycerol estersFinancial compensationG-Protein-Coupled ReceptorsGTP-Binding Protein alpha Subunits, GsGTP-Binding ProteinsGene ExpressionGenesGeneticGenetic TranscriptionGenotypeHealthHigh Fat DietHumanImmune systemImpairmentIndividualInfiltrationInflammationInsulinInsulin ResistanceKnockout MiceLeadLinkLipidsMetabolicMetabolic stressMicronutrientsMusNon-Insulin-Dependent Diabetes MellitusObesityPancreasPharmaceutical PreparationsPharmacologyPhysiologicalPlacental LactogenPlayProstaglandin E ReceptorProtein IsoformsProteinsPublic HealthReceptor InhibitionRegulationRisk FactorsRoleSignal PathwaySignal TransductionStimulusStructure of beta Cell of isletTissuesUnited StatesWorkblood glucose regulationcell regenerationcell typecohortdiabeticdietary controlexhaustionexperimental studyfeedingimprovedin vivoinsulin secretionisletmacrophagemouse modelnecrotic tissueoverexpressionpreventpromoterreceptorresponsesingle-cell RNA sequencingtooltranscription factor
中文摘要
翻译
项目总结/文摘
英文摘要
Project summary/Abstract
Type 2 diabetes is a major health concern in the United States. It occurs when individuals fail to compensate
for an increased demand for insulin from the pancreatic β cells. The prostaglandin E receptor EP3 (encoded by
Ptger3), which responds to prostaglandin E2 (PGE2), has been shown to inhibit insulin secretion. EP3 is
upregulated in diabetic individuals and with age. Data from our lab has demonstrated that ex vivo
pharmacological inhibition of EP3 increases β cell mass and survival. The role of EP3 specifically in the β cell
has not been examined. I propose using a β-cell-specific EP3 KO mouse model to determine the effect of EP3
inactivation in the context of high fat diet. In addition, FoxM1 is a transcription factor necessary for β cell
proliferation. FoxM1 levels decrease with age while EP3 levels increase. In this proposal, I outline experiments
to elucidate what role, if any, FoxM1 has in regulating Ptger3 expression.
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