Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Research Glucose sensing in the pancreatic beta cell: a computational systems analysis. | Fridlyand and Philipson Theoretical Biology and Medical Modelling 2010 7 15 http content 7 1 15 THEORETICAL BIOLOGY AND MEDICAL MODELLING RESEARCH Open Access Glucose sensing in the pancreatic beta cell a computational systems analysis Leonid E Fridlyand and Louis H Philipson Correspondence lfridlia@ 1 Department of Medicine The University of Chicago Chicago IL USA 60637 Full list of author information is available at the end of the article 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 .
