Modeling and Analysis of Multimodal Bursting in Pancreatic Beta-Cells

胰腺β细胞多模态爆发的建模和分析

• 批准号: 9981822
• 负责人: Richard Bertram
• 金额: $ 7.82万
• 依托单位: Florida State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9981822&HistoricalAwards=false
• 关键词: Modeling; Analysis; Multimodal; Bursting; Pancreatic

Bertram9981822 The investigator uses mathematical models to study dynamicaland biophysical mechanisms for the multiple modes of burstingobserved in pancreatic Beta-cells. In pancreatic islets,Beta-cells burst with a period of 10-30 seconds, while isolatedBeta-cells burst with periods of either 2-5 seconds or 1-2minutes. The primary goal of this project is to answer thefollowing questions: (1) How does a single oscillator (theBeta-cell) produce such a wide range of bursting behaviors? (2)What biophysical mechanisms drive the different modes ofbursting? (3) Why does the bursting behavior differ betweenisolated cells and intact islets? To address these questions theinvestigator develops a family of mathematical models thatemploy several slow variables. He studies how well these modelsreproduce key electrophysiological and calcium imaging data fromisolated Beta-cells, cell clusters, and intact islets. Pancreatic Beta-cells are the only cells in the human bodythat secrete insulin, a hormone required by other cells toprocess sugars in the blood. If Beta-cells function improperlythen late-onset diabetes occurs, the most common form ofdiabetes. Insulin is secreted from Beta-cells when the cellsgenerate electrical impulses, so understanding the electricalactivity of Beta-cells is crucial to understanding insulinsecretion. For many years mathematical models have providedinsight into the complex electrical behavior of Beta-cells. Inthe current project, the investigator develops improvedmathematical models to understand how Beta-cells produce patternsof electrical impulses that are key to normal insulin secretion.Only when these normal patterns are understood can abnormalelectrical activity, and abnormal insulin secretion resulting indiabetes, be understood.

Bertram9981822 研究人员使用数学模型来研究在胰腺 Beta 细胞中观察到的多种爆发模式的动力学和生物物理机制。 在胰岛中，β 细胞的爆发周期为 10-30 秒，而孤立的 β 细胞的爆发周期为 2-5 秒或 1-2 分钟。 该项目的主要目标是回答以下问题：（1）单个振荡器（β-cell）如何产生如此广泛的爆发行为？ (2)什么生物物理机制驱动不同的爆发模式？ (3) 为什么分离的细胞和完整的胰岛的破裂行为不同？ 为了解决这些问题，研究人员开发了一系列使用多个慢变量的数学模型。 他研究这些模型如何很好地再现来自分离的β细胞、细胞簇和完整胰岛的关键电生理学和钙成像数据。 胰腺β细胞是人体内唯一分泌胰岛素的细胞，胰岛素是其他细胞处理血液中糖所需的激素。 如果β细胞功能不正常，就会发生迟发性糖尿病，这是最常见的糖尿病形式。 当β细胞产生电脉冲时，胰岛素就会分泌出来，因此了解β细胞的电活动对于了解胰岛素分泌至关重要。 多年来，数学模型提供了对 Beta 细胞复杂电行为的深入了解。 在当前的项目中，研究人员开发了改进的数学模型，以了解β细胞如何产生对正常胰岛素分泌至关重要的电脉冲模式。只有了解这些正常模式，才能了解异常电活动和导致糖尿病的异常胰岛素分泌。