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.

研究者使用数学模型来研究在胰腺β细胞中观察到的多种爆发模式的动态和生物物理机制。在胰岛中，β细胞的破裂周期为10-30秒，而分离的β细胞的破裂周期为2-5秒或1-2分钟。这个项目的主要目标是回答以下问题：(1)单个振荡器（β细胞）如何产生如此广泛的爆发行为？(2)驱动不同爆发模式的生物物理机制是什么？(3)为什么分离细胞和完整胰岛的破裂行为不同？为了解决这些问题，研究者开发了一系列采用几个慢变量的数学模型。他研究了这些模型如何从分离的β细胞、细胞簇和完整的胰岛上复制关键的电生理和钙成像数据。胰腺β细胞是人体中唯一分泌胰岛素的细胞，胰岛素是其他细胞处理血液中糖分所必需的一种激素。如果β细胞功能不正常，就会发生迟发性糖尿病，这是糖尿病最常见的形式。胰岛素是由β细胞产生电脉冲时分泌的，因此了解β细胞的电活动对了解胰岛素分泌至关重要。多年来，数学模型为β细胞复杂的电行为提供了洞见。在目前的项目中，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。只有理解了这些正常的模式，才能理解异常的电活动和导致糖尿病的异常胰岛素分泌。