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.

研究者和他的同事们研究分泌胰岛素的胰腺细胞的行为。这些细胞表现出广泛的复杂动态，最好借助数学建模和分析来理解。研究者最近开发了一种新的β细胞数学模型，该模型假设在内质网和细胞膜之间存在细胞内钙亚空间。该模型基于一个合作实验室的最新数据，并随着新实验的进行而进一步发展。一个发展方向涉及研究复杂的电爆发模式，通常在胰岛和分离的β细胞中观察到。研究者通过数学建模确定这些复杂节律是否是由于糖酵解中的振荡引起的——也就是说，膜驱动的破裂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。一个关键的问题是这些涉及糖酵解节律的振荡器是否可以通过电偶联来同步。这是一个必要条件，因为β细胞在胰岛中是电偶联的。最后，研究了单细胞模型和胰岛模型中随机噪声的影响。通道噪声在单个β细胞的电模式中是明显的，并且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破裂模式中起关键作用。由β细胞组成的胰岛的研究很重要，原因有很多。从临床角度来看，它们是正常葡萄糖稳态的关键参与者。因为β细胞是体内唯一能制造和分泌胰岛素的细胞，它们的功能失调会导致II型糖尿病或晚期糖尿病，这是糖尿病最常见的形式。要了解是什么使细胞发生故障，首先必须了解它们的正常功能，这是这项工作的主要目的。从非生物学的角度来看，β细胞作为许多生物化学和细胞过程的焦点而引起了极大的兴趣。它们在许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细胞的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，只有借助于数学才能真正理解。对β细胞的建模和分析产生了新的数学方法，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重要接口的研究机会。