Targeting alpha-cell GPCRs to stimulate glucagon and counter hypoglycemia
靶向 α 细胞 GPCR 刺激胰高血糖素并对抗低血糖
基本信息
- 批准号:10675646
- 负责人:
- 金额:$ 10.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-30 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdrenal GlandsAlanineAlpha CellAmino AcidsArginineAutomobile DrivingAwarenessBiological AssayBiologyBlood GlucoseBrainCarbohydratesCarbonCatecholaminesCell CommunicationCell physiologyCellsClinicalCognitionComplexComplicationDangerousnessDiabetes MellitusDoseDropsEmergency SituationEmergency treatmentEnergy-Generating ResourcesEtiologyExposure toFoundationsFunctional disorderG-Protein-Coupled ReceptorsGastric Inhibitory PolypeptideGenerationsGlassGlucagonGlucoseHepaticHumanHydrocortisoneHypoglycemiaImpairmentIngestionInsulinInsulin-Dependent Diabetes MellitusLabelLifeMeasuresMetabolicMetabolismMethodsModelingMolecularMusNeuronsNon obesePathway interactionsPatientsPersonsPhysiologicalPhysiologyRecurrenceResearch PersonnelScheduleSerious Adverse EventStimulusStrenuous ExerciseStreptozocinSystemTechnical ExpertiseTestingTherapeuticVariantWineWorkcareercounterregulationdesigndiabeticeffective therapyeffectiveness evaluationgastric inhibitory polypeptide receptorglucose outputglycemic controlin vivoinsightinsulin secretionisletmouse modelnovelnovel strategiespreventresponseside effect
项目摘要
PROJECT SUMMARY
Hypoglycemia is a dangerous complication of exogenous insulin therapy in Type 1 Diabetes (T1D) that is treated
by exogenous glucagon secretion. However, the use of exogenous glucagon has its own side effects and can
be complicated to administer in an emergency situation. As an alternative, stimuli that lead to robust endogenous
glucagon secretion could be effective to counter severe hypoglycemia. Glucagon secretion can be stimulated by
amino acids, like alanine and arginine, as well as by glucose-dependent insulinotropic peptide (GIP).
Remarkably, we found that while alanine or GIP alone induce modest increases in glucagon secretion, the
combination of alanine and GIP synergistically increase glucagon secretion in both isolated mouse and human
islets, as well as mice in vivo. A better understanding of the physiology of this glucagon and the mechanism of
its release is needed to determine if stimulating endogenous glucagon can treat hypoglycemia in T1D. We
hypothesize that endogenous -cell stimuli, such as GIP + alanine, can counter insulin-induced hypoglycemia.
The aims of this project are designed to elucidate whether -cell stimuli can mitigate severe hypoglycemia, how
the effects of -cell stimulation are changed in T1D, and what is the mechanism that alanine stimulates the -
cell to secrete glucagon. Successful completion of this project will enhance our understanding of the -cell and
provide insight for the basis of therapeutics for hypoglycemia or insulin co-therapies. In addition, the aims will
broaden the Candidate’s technical expertise and develop conceptual understanding of -cell physiology that will
provide a foundation for a career as an independent investigator.
项目总结
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Discovery of a potent GIPR peptide antagonist that is effective in rodent and human systems.
- DOI:10.1016/j.molmet.2022.101638
- 发表时间:2022-12
- 期刊:
- 影响因子:8.1
- 作者:Yang, Bin;Gelfanov, Vasily M.;El, Kimberley;Chen, Alex;Rohlfs, Rebecca;DuBois, Barent;Hansen, Ann Maria Kruse;Perez-Tilve, Diego;Knerr, Patrick J.;'Alessio, David;Campbell, Jonathan E.;Douros, Jonathan D.;Finan, Brian
- 通讯作者:Finan, Brian
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Kimberley M El其他文献
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{{ truncateString('Kimberley M El', 18)}}的其他基金
Targeting alpha-cell GPCRs to stimulate glucagon and counter hypoglycemia
靶向 α 细胞 GPCR 刺激胰高血糖素并对抗低血糖
- 批准号:
10427574 - 财政年份:2022
- 资助金额:
$ 10.57万 - 项目类别:
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