Investigations to Assess the Role of Glucagon Signaling in Healthspan and Aging
Investigations to Assess the Role of Glucagon Signaling in Healthspan and Aging
批准号:
9384942
负责人:
JENNIFER HELENE STERN
金额:
$10.75万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-08-15 至 2019-07-31
关键词:
AddressAdipocytesAdipose tissueAdvocateAgeAgingAntidiabetic DrugsBehavioral AssayBiology of AgingCaloric RestrictionCharacteristicsClosure by clampCognitiveDataDepressed moodDevelopmentDiabetes MellitusDiseaseDoctor of PhilosophyEnergy MetabolismFoundationsFunctional disorderGenetic ModelsGlucagonGlucagon ReceptorGrantHepaticHepatocyteHigh PrevalenceHomeostasisHyperglycemiaHyperinsulinismImpairmentIncidenceInsulinInsulin ResistanceInterventionInvestigationKnowledgeLaboratoriesLongevityMentorsMetabolicMetabolic ControlMetabolismMetforminModelingMonitorMotorMusNon-Insulin-Dependent Diabetes MellitusObese MiceObesityPathway interactionsPhasePlayPopulationReceptor SignalingResearchRiskRoleSignal PathwaySignal TransductionSignaling MoleculeThinnessTissuesTrainingWeightWorkadenylate kinaseage groupage relatedblood glucose regulationglucose outputglucose productionhealthy aginghuman old age (65+)hyperglucagonemiaimprovedinsulin signalingnovel therapeuticsresponse
中文摘要
随着人口老龄化,2型糖尿病(T2DM)的发病率持续上升,几乎是1999年的两倍
英文摘要
As our population ages, the incidence of Type II diabetes mellitus (T2DM) continues to rise, nearly doubling from
the age of 45 to 65. T2DM is characterized by both hyperinsulinemia and hyperglucagonemia. The majority of
research in the metabolic field has focused on the hyperinsulinemia that is characteristic of this disease.
However, inhibition of glucagon action is highly effective in treating T2DM. In fact, metformin, the most prescribed
anti-diabetic drug, activates AMP Kinase (AMPK) to inhibit hepatic glucagon signaling and limit hepatic glucose
production in T2DM. Similar to the metabolic field, research focused on the accelerated aging in T2DM has
primarily examined the role of hyperinsulinemia. Interventions and genetic models which decrease insulin
signaling enhance lifespan, alter energy metabolism, and decrease age-related diseases in the mouse. Despite
the hyperglycemia of T2DM and essential role of glucagon receptor signaling in the long-term survival of the lean
aging mouse, we lack knowledge of the role glucagon plays in the accelerated aging of obesity or the slowed
aging resulting from calorie restriction (CR). The widespread use and development of new therapeutics that
inhibit glucagon signaling to treat T2DM demand studies focused on the role of glucagon signaling in healthy
aging. I propose 3 aims focused on the role of global, hepatocyte, and adipocyte glucagon signaling in metabolic
control and progression of aging in lean, obese, and calorie restricted mice. The studies proposed in this grant
will be the first that investigate the role of glucagon signaling in healthspan, assess the response to elimination
of glucagon signaling in either the adipocyte or hepatocyte, and address the potential for alternative responses
to glucagon signaling inhibition in obesity, normal weight, and calorie restriction.
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Investigations to Assess the Role of Glucagon Signaling in Healthspan and Aging
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批准号:9791315
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项目类别:
-
资助金额:$24.7万
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财政年份:2017
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负责人:JENNIFER HELENE STERN
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依托单位:
Investigations to Assess the Role of Glucagon Signaling in Healthspan and Aging
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批准号:10600274
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项目类别:
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资助金额:$12.0万
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财政年份:2017
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负责人:JENNIFER HELENE STERN
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依托单位:
国内基金
海外基金
支链氨基酸代谢紊乱调控“Adipocytes - Macrophages Crosstalk”诱发2型糖尿病脂肪组织功能和结构障碍的作用及机制
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批准号:81970721
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项目类别:面上项目
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资助金额:55.0万元
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批准年份:2019
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负责人:陶凌
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依托单位: