BIOMD0000000349
type: SBMLModel
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is described by: http://identifiers.org/pubmed/20497556
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occurs in: http://identifiers.org/taxonomy/9606
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notes: This a model from the article: Glucose sensing in the pancreatic beta cell: a computational systems analysis. Fridlyand LE, Philipson LH. Theor Biol Med Model. 2010 May 24;7:15. 20497556 , Abstract: BACKGROUND: Pancreatic beta-cells respond to rising blood glucose by increasing oxidative metabolism, leading to an increased ATP/ADP ratio in the cytoplasm. This leads to a closure of KATP channels, depolarization of the plasma membrane, influx of calcium and the eventual secretion of insulin. Such mechanism suggests that beta-cell metabolism should have a functional regulation specific to secretion, as opposed to coupling to contraction. The goal of this work is to uncover contributions of the cytoplasmic and mitochondrial processes in this secretory coupling mechanism using mathematical modeling in a systems biology approach. METHODS: We describe a mathematical model of beta-cell sensitivity to glucose. The cytoplasmic part of the model includes equations describing glucokinase, glycolysis, pyruvate reduction, NADH and ATP production and consumption. The mitochondrial part begins with production of NADH, which is regulated by pyruvate dehydrogenase. NADH is used in the electron transport chain to establish a proton motive force, driving the F1F0 ATPase. Redox shuttles and mitochondrial Ca2+ handling were also modeled. RESULTS: The model correctly predicts changes in the ATP/ADP ratio, Ca2+ and other metabolic parameters in response to changes in substrate delivery at steady-state and during cytoplasmic Ca2+ oscillations. Our analysis of the model simulations suggests that the mitochondrial membrane potential should be relatively lower in beta cells compared with other cell types to permit precise mitochondrial regulation of the cytoplasmic ATP/ADP ratio. This key difference may follow from a relative reduction in respiratory activity. The model demonstrates how activity of lactate dehydrogenase, uncoupling proteins and the redox shuttles can regulate beta-cell functio…
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substance units: 292482
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name: Fridlyand2010_GlucoseSensitivity_B
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W3 CDTF: Tue Aug 09 19:27:55 BST 2011

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W3 CDTF: Fri Mar 09 16:18:04 GMT 2012

ORG:
  orgname: EMBL-EBI
n:
  given: Ishan
  family: Ajmera