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- W2039075498 abstract "Glucagon, a 29-amino acid hormone secreted from the alpha-cells of the islets of the endocrine pancreas, is critical for blood glucose homeostasis by promoting liver production of glucose in hypoglycemia. A clearly defined, testable model for alpha cell glucagon secretion is lacking. Alpha-cells respond to rising blood glucose by increasing oxidative metabolism, closing ATP-sensitive K+ channels and the resulting depolarization of the plasma membrane leads to decreased glucagon secretion. This mechanism of glucose sensing involves the coupling of electrophysiological, cytoplasmic and mitochondrial processes. Here we describe a computational systems analysis of pancreatic alpha-cells including metabolic processes, electrical activity and Ca2+ dynamics in the regulation of glucagon secretion. This mathematical model of alpha-cell sensitivity to glucose is based on a previous model for pancreatic beta-cells. We also formulated a Hodgkin-Huxley-type ionic model for action potentials in alpha-cells that incorporates voltage-gated Ca2+, K+, Na+ and Cl- currents. The metabolic and ionic models are coupled to the equations describing intracellular Ca2+ homeostasis and glucagon secretion that depends on an activation of specific voltage-gated Ca2+ channels. This model simulates the behavior of alpha-cell action potentials under a wide range of experimental conditions, including block of action potential firing at increased glucose levels or due to channel blockade. Paracrine regulation of glucagon secretion can be modeled following the effects of gamma aminobutyric acid or somatostatin secreted by other islet cells on corresponding alpha-cell ion channels and metabolism. This computational systems analysis aids in providing a more complete understanding of the complex process of alpha-cell glucose sensing and the pathways of treatment of diabetes." @default.
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- W2039075498 date "2012-01-01" @default.
- W2039075498 modified "2023-09-26" @default.
- W2039075498 title "Computational Systems Analysis of Glucose Sensitivity, Electrical Activity and Glucagon Secretion in Pancreatic Alpha-Cells" @default.
- W2039075498 doi "https://doi.org/10.1016/j.bpj.2011.11.751" @default.
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