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• W2183616069 endingPage "e1004600" @default.
• W2183616069 startingPage "e1004600" @default.
• W2183616069 abstract "Intestinal L-cells sense glucose and other nutrients, and in response release glucagon-like peptide 1 (GLP-1), peptide YY and other hormones with anti-diabetic and weight-reducing effects. The stimulus-secretion pathway in L-cells is still poorly understood, although it is known that GLP-1 secreting cells use sodium-glucose co-transporters (SGLT) and ATP-sensitive K+-channels (K(ATP)-channels) to sense intestinal glucose levels. Electrical activity then transduces glucose sensing to Ca2+-stimulated exocytosis. This particular glucose-sensing arrangement with glucose triggering both a depolarizing SGLT current as well as leading to closure of the hyperpolarizing K(ATP) current is of more general interest for our understanding of glucose-sensing cells. To dissect the interactions of these two glucose-sensing mechanisms, we build a mathematical model of electrical activity underlying GLP-1 secretion. Two sets of model parameters are presented: one set represents primary mouse colonic L-cells; the other set is based on data from the GLP-1 secreting GLUTag cell line. The model is then used to obtain insight into the differences in glucose-sensing between primary L-cells and GLUTag cells. Our results illuminate how the two glucose-sensing mechanisms interact, and suggest that the depolarizing effect of SGLT currents is modulated by K(ATP)-channel activity. Based on our simulations, we propose that primary L-cells encode the glucose signal as changes in action potential amplitude, whereas GLUTag cells rely mainly on frequency modulation. The model should be useful for further basic, pharmacological and theoretical investigations of the cellular signals underlying endogenous GLP-1 and peptide YY release." @default.
• W2183616069 created "2016-06-24" @default.
• W2183616069 creator A5030956192 @default.
• W2183616069 creator A5046138635 @default.
• W2183616069 date "2015-12-02" @default.
• W2183616069 modified "2023-10-18" @default.
• W2183616069 title "Mathematical Modeling of Interacting Glucose-Sensing Mechanisms and Electrical Activity Underlying Glucagon-Like Peptide 1 Secretion" @default.
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• W2183616069 doi "https://doi.org/10.1371/journal.pcbi.1004600" @default.
• W2183616069 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4667885" @default.
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• W2183616069 hasPublicationYear "2015" @default.
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