Metabolic regulation of pancreatitis
胰腺炎的代谢调节
基本信息
- 批准号:10028137
- 负责人:
- 金额:$ 36.23万
- 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
- 起止时间:2020-07-01 至 2024-02-28
- 项目状态:已结题
- 来源:
- 关键词:Acinar CellAcinus organ componentAdenosine TriphosphateAffectAlcohol consumptionAlcoholic PancreatitisAlcoholsAnimal ModelAnimalsCaeruleinCalciumCellsClinicalClinical DataClinical TrialsDataDevelopmentDietDiseaseEnzyme ActivationEstersEthanolExocrine pancreasExperimental ModelsFailureFatty AcidsHealthHumanHypophosphatemiaImpairmentIn VitroInjuryInvestigationLeadMediatingMetabolicMitochondriaModelingMusOrganOrganellesPancreasPancreatic InjuryPancreatic ductPancreatitisPathogenesisPatientsPreventionProductionProtein BiosynthesisRegulationRisk FactorsRoleSerumSeveritiesSeverity of illnessStudy modelsSupplementationTestingTranslatingUnited Statesabsorptionacute pancreatitisalcohol effectalcohol induced pancreatic injuryalcohol preventioncell injurychronic pancreatitisdesigneffective therapyfeedinghuman diseaseimprovedinorganic phosphatemitochondrial dysfunctionmortalitymouse modelnovelpre-clinicalprematurepressurepreventproblem drinkerprotective effectrestoration
项目摘要
Abstract
Acute pancreatitis is a debilitating disease that affects more than 280,000 people in the United States. A
hallmark of acute pancreatitis is systemic injury and multi-organ failure leading to mortality in 3-20% of
patients. There are currently no treatments for acute pancreatitis. Alcohol consumption is a major cause of
human acute pancreatitis and despite intensive investigation the pathogenesis of alcohol-induced pancreatitis
remains poorly understood. Evidence suggests that acinar cell injury is associated with mitochondrial
dysfunction leading to ATP depletion and prevention of mitochondrial damage or restoration of mitochondrial
function may limit pancreatitis. Phosphate availability is required for ATP synthesis. Clinical
hypophosphatemia is common in alcoholic patients and alcohol itself impairs dietary phosphate absorption. In
preliminary studies, we discovered that reduced serum phosphate levels in patients with acute pancreatitis are
associated with increased pancreatitis severity. We proposed that reduced phosphate availability may
predispose to alcohol-induced pancreatic injury and may be central to the development of alcoholic
pancreatitis. Our preliminary data indicate that alcohol rapidly induces pancreatitis when mice are fed a low
phosphate diet, consistent with the concept that hypophosphatemia sensitizes the pancreas to alcohol. The
current study is designed to test the hypothesis that alcohol-induced pancreatitis can be ameliorated by
phosphate administration. We will determine the contribution of hypophosphatemia to pancreatitis severity, the
protective effects of phosphate treatment in mouse models of pancreatitis, and the mechanisms underlying the
effects of hypophosphatemia on pancreatic injury. Successful completion of these studies will yield compelling
pre-clinical data for a novel, simple and effective treatment for pancreatitis that will provide the basis for a
clinical trial in humans.
抽象的
急性胰腺炎是一种使人衰弱的疾病,影响了美国280,000多人。一个
急性胰腺炎的标志是系统性损伤和多器官失败,导致3-20%的死亡率
患者。目前尚无急性胰腺炎的治疗方法。饮酒是主要原因
人类急性胰腺炎,尽管进行了深入研究,但酒精引起的胰腺炎的发病机理
仍然很了解。有证据表明腺泡细胞损伤与线粒体有关
功能障碍导致ATP耗竭和预防线粒体损伤或线粒体的恢复
功能可能限制胰腺炎。 ATP合成需要磷酸盐可用性。临床
低磷酸血症在酒精患者中很常见,酒精本身会损害饮食中的磷酸盐吸收。在
初步研究,我们发现急性胰腺炎患者的血清磷酸盐水平降低是
与胰腺炎的严重程度增加有关。我们提出降低的磷酸盐可用性可能
易于酒精引起的胰腺损伤,可能是酗酒的核心
胰腺炎。我们的初步数据表明,当小鼠喂养小鼠时,酒精会迅速诱导胰腺炎
磷酸盐饮食,与低磷酸血症使胰腺对酒精敏感的概念一致。这
当前的研究旨在检验以下假设:酒精诱导的胰腺炎可以通过
磷酸盐给药。我们将确定低磷酸血症对胰腺炎严重程度的贡献,
磷酸盐治疗在胰腺炎的小鼠模型中的保护作用,以及依据的机制
低磷酸血症对胰腺损伤的影响。这些研究的成功完成将产生引人注目的
用于胰腺炎的新颖,简单有效治疗的新型,简单有效治疗的临床前数据,这将为A提供基础
人类的临床试验。
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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Rodger A. Liddle其他文献
318 - The Pressure Sensitive Ion Channel, PIEZO1, Induces Enzyme Activation through Sustained Cytosolic Calcium Elevation in Pancreatic Acinar Cells
- DOI:
10.1016/s0016-5085(18)30713-3 - 发表时间:
2018-05-01 - 期刊:
- 影响因子:
- 作者:
Sandip M. Swain;Joelle Romac;Rafiq A. Shahid;Stephen J. Pandol;Rodger A. Liddle - 通讯作者:
Rodger A. Liddle
Tu1198: INITIATION AND SEVERITY OF EXPERIMENTAL PANCREATITIS ARE MODIFIED BY PHOSPHATE
- DOI:
10.1016/s0016-5085(22)62161-9 - 发表时间:
2022-05-01 - 期刊:
- 影响因子:
- 作者:
Ahmad Farooq;Liliana C. Hernandez;Sandip M. Swain;Joelle Romac;Steven Vigna;Rodger A. Liddle - 通讯作者:
Rodger A. Liddle
Mo1929 - Dietary Regulation of Enteroendocrine Cell Function is Microbiota Dependent
- DOI:
10.1016/s0016-5085(17)32846-9 - 发表时间:
2017-04-01 - 期刊:
- 影响因子:
- 作者:
Lihua Ye;Rodger A. Liddle;John F. Rawls - 通讯作者:
John F. Rawls
27 The Ultrastructure of the Enteroendocrine Cell Revealed in Three Dimensions
- DOI:
10.1016/s0016-5085(13)60023-2 - 发表时间:
2013-05-01 - 期刊:
- 影响因子:
- 作者:
Diego V Bohorquez;Andrew Roholt;Satish Medicetty;Rodger A. Liddle - 通讯作者:
Rodger A. Liddle
29 Immunoglobulin-Like Domain Containing Receptor Mediates Fat-Stimulated Cholecystokinin Secretion
- DOI:
10.1016/s0016-5085(13)60025-6 - 发表时间:
2013-05-01 - 期刊:
- 影响因子:
- 作者:
Rashmi Chandra;Yu Wang;Rafiq A. Shahid;Steven R. Vigna;Neil J. Freedman;Rodger A. Liddle - 通讯作者:
Rodger A. Liddle
Rodger A. Liddle的其他文献
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{{ truncateString('Rodger A. Liddle', 18)}}的其他基金
Mechanisms of mechanically-induced acute pancreatitis
机械性急性胰腺炎的机制
- 批准号:
10538561 - 财政年份:2019
- 资助金额:
$ 36.23万 - 项目类别:
Mechanisms of mechanically-induced acute pancreatitis
机械性急性胰腺炎的机制
- 批准号:
10320376 - 财政年份:2019
- 资助金额:
$ 36.23万 - 项目类别:
The role of gut endocrine cells in Parkinson's Disease
肠道内分泌细胞在帕金森病中的作用
- 批准号:
9234533 - 财政年份:2016
- 资助金额:
$ 36.23万 - 项目类别:
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