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研究者使用数学模型来研究胰腺β细胞中多种爆发模式的动力学和生物物理机制。 在胰岛中，β细胞的爆发为10-30秒，而隔离的贝塔细胞爆发，周期为2-5秒或1-2分钟。 该项目的主要目标是回答关注问题的问题：（1）单个振荡器（thebeta-cell）如何产生如此广泛的爆发行为？ （2）哪些生物物理机制驱动了爆发的不同模式？ （3）为什么分离的细胞和完整的胰岛之间的破裂行为有所不同？ 为了解决这些问题，Investigator开发了一个数学模型的家族，该模型使几个慢速变量。 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产生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，这是其他细胞在血液中造成的激素。 如果发生β细胞的功能不当发生晚期发作的糖尿病，则是糖尿病最常见的形式。 当细胞创收电脉冲时，胰岛素是从β细胞中分泌的，因此理解β细胞的电动性对于理解胰岛素分泌至关重要。 多年来，数学模型已提供了β细胞的复杂电气行为的视觉。 在当前的项目中，研究者开发了改进的数学模型，以了解β细胞如何产生电脉冲的模式，这是正常胰岛素分泌的关键。仅当理解这些正常模式时，就可以理解异常的胰岛素活性，并理解导致印度胰岛素的异常分泌。