A computational systems analysis of factors regulating α cell glucagon secretion.
A computational systems analysis of factors regulating α cell glucagon secretion.
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DOI：
10.4161/isl.22193
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发表时间：
2012-07
期刊：
影响因子：
2.2
通讯作者：
Philipson LH
中科院分区：
文献类型：
--
作者：
Fridlyand LE;Philipson LH
胰升糖素是一种由胰岛α细胞分泌的多肽激素，对血糖动态平衡至关重要。为了更好地理解这些过程，我们回顾了文献，并采用了细胞内代谢和胰高血糖素分泌的电调节的计算系统分析。α细胞代谢参数的数学模型是基于我们先前针对胰腺β细胞的模型。我们还建立了包含钙离子、钾离子、钠离子和氯离子电流的动作电位离子模型。代谢和离子模型被耦合到描述钙稳态和依赖于特定电压门控钙通道激活的胰高血糖素分泌的方程。分析了旁分泌和内分泌调节，重点分析了它们对膜电位超极化的影响。这个通用模型模拟并洞察了在广泛的实验条件下对胰升糖素分泌的调节机制。我们还回顾和分析了α细胞的功能失调机制，以确定调节1型和2型糖尿病患者胰高血糖素分泌的关键药理学靶点。
Glucagon, a peptide hormone secreted from the α-cells of the pancreatic islets, is critical for blood glucose homeostasis. We reviewed the literature and employed a computational systems analysis of intracellular metabolic and electrical regulation of glucagon secretion to better understand these processes. The mathematical model of α-cell metabolic parameters is based on our previous model for pancreatic β-cells. We also formulated an ionic model for action potentials that incorporates Ca2+, K+, Na+ and Cl- currents. Metabolic and ionic models are coupled to the equations describing Ca2+ homeostasis and glucagon secretion that depends on activation of specific voltage-gated Ca2+ channels. Paracrine and endocrine regulations were analyzed with an emphasis on their effects on a hyperpolarization of membrane potential. This general model simulates and gives insight into the mechanisms of regulation of glucagon secretion under a wide range of experimental conditions. We also reviewed and analyzed dysfunctional mechanisms in α-cells to determine key pharmacological targets for modulating glucagon secretion in type 1 and 2 diabetes.
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影响因子：
--
作者：
Bertram, Richard;Sherman, Arthur;Satin, Leslie S.
通讯作者：
Satin, Leslie S.
影响因子：
5.5
作者：
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影响因子：
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DOI：
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发表时间：
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影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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