Phantom Bursting Models and Complex Bursting Patterns in Pancreatic Islets

胰岛的幻影破裂模型和复杂破裂模式

• 批准号: 0311856
• 负责人: Richard Bertram
• 金额: $ 12.73万
• 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: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0311856&HistoricalAwards=false
• 关键词: Phantom; Bursting; Models; Complex; Patterns

Bertram The investigator and his colleagues study the behavior ofinsulin-secreting pancreatic beta-cells. These cells display awide range of complex dynamics that are best understood with theaid of mathematical modeling and analysis. The investigator hasrecently developed a new mathematical model for beta-cells thatpostulates an intracellular calcium subspace compartment locatedbetween the endoplasmic reticulum and the cell membrane. Thismodel is based on recent data from a collaborating lab, and isbeing further developed as new experiments are performed. Onedirection of development involves the investigation of complexelectrical bursting patterns that are often observed inpancreatic islets and isolated beta-cells. The investigatordetermines, through mathematical modeling, whether these complexrhythms are due to oscillations in glycolysis -- that is, whetherthe coexistence of a membrane-driven bursting oscillator and anendogenous glycolytic oscillator is consistent with the publisheddata, and with data from collaborating labs. One key questionthat is addressed is whether these oscillators involvingglycolytic rhythms can be synchronized by electrical coupling.This is a necessary condition since beta-cells are electricallycoupled in islets. Finally, the effects of stochasticity throughchannel noise are investigated in both single-cell and isletmodels. Channel noise is evident in the electrical patterns ofsingle beta-cells, and suppression of this noise throughelecrical coupling may play a key role in the more regular andslower bursting patterns observed in islets. The study of pancreatic islets, composed of beta-cells, isimportant for a number of reasons. From a clinical viewpoint,they are key players in normal glucose homeostasis. Becausebeta-cells are the only cells in the body that make and secreteinsulin, their malfunction leads to type II or late-onsetdiabetes, the most prevalent form of the disease. To understandwhat makes the cells malfunction, one must first understand theirnormal functioning, which is the primary aim of this work. From abiological viewpoint, beta-cells are of great interest as thefocal point of a number of biochemical and cellular processes.They are similar in many ways to neurons, but have more complexbiochemical regulatory mechanisms. Thus, information gained fromthe study of beta-cells largely transfers over to neurons, aswell as other secretory cells. Finally, from a mathematicalviewpoint, beta-cells display rich dynamics that can only trulybe understood with the aid of mathematics. Modeling and anlysisof beta-cells has led to new mathematics, most of which can andis being applied to the study of other bursting nerve andendocrine cells. The investigator involves graduate andundergraduate students in the project, providing them withresearch opportunities at the important interface betweenbiological and mathematical sciences.

Bertram 研究员和他的同事研究分泌胰岛素的胰腺 β 细胞的行为。 这些细胞表现出广泛的复杂动态，借助数学建模和分析可以最好地理解这些动态。 研究人员最近开发了一种新的β细胞数学模型，该模型假设细胞内钙亚空间隔室位于内质网和细胞膜之间。 该模型基于合作实验室的最新数据，并且随着新实验的进行而得到进一步开发。 发展的一个方向涉及对复杂的电爆发模式的研究，这种模式经常在胰岛和分离的β细胞中观察到。 研究人员通过数学模型确定这些复杂的节律是否是由于糖酵解中的振荡引起的——也就是说，膜驱动的爆发振荡器和内源性糖酵解振荡器的共存是否与已发表的数据以及合作实验室的数据一致。 需要解决的一个关键问题是这些涉及糖酵解节律的振荡器是否可以通过电耦合来同步。这是一个必要条件，因为β细胞在胰岛中是电耦合的。 最后，在单细胞和胰岛模型中研究了通道噪声的随机性影响。 通道噪声在单个β细胞的电模式中很明显，通过电耦合抑制这种噪声可能在胰岛中观察到的更规则和更慢的爆发模式中发挥关键作用。 出于多种原因，对由 β 细胞组成的胰岛的研究很重要。 从临床角度来看，它们是正常葡萄糖稳态的关键参与者。 由于β细胞是体内唯一制造和分泌胰岛素的细胞，它们的功能障碍会导致II型或迟发性糖尿病，这是该疾病最常见的形式。 要了解细胞发生故障的原因，必须首先了解它们的正常功能，这是这项工作的主要目标。 从生物学的角度来看，β细胞作为许多生化和细胞过程的焦点而引起人们极大的兴趣。它们在很多方面与神经元相似，但具有更复杂的生化调节机制。 因此，从β细胞研究中获得的信息大部分转移到神经元以及其他分泌细胞。 最后，从数学的角度来看，β细胞表现出丰富的动态，只有借助数学才能真正理解。 β细胞的建模和分析催生了新的数学，其中大部分可以并且正在应用于其他破裂神经和内分泌细胞的研究。 研究者让研究生和本科生参与该项目，为他们提供在生物科学和数学科学之间的重要交叉点上的研究机会。