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• W4380423149 endingPage "1883" @default.
• W4380423149 startingPage "1871" @default.
• W4380423149 abstract "Objective This study aimed to investigate the possible mechanisms by which orphan G protein-coupled receptor GPR41 activation enhances glucose uptake into C2C12 myotubes using a GPR41-selective agonist, AR420626, and to examine the ability of this agent to improve insulin sensitivity and glucose homeostasis in vivo. Methods Basal and insulin-stimulated glucose uptake and glucose transporter 4 translocations were measured in C2C12 myotubes. Ca2+ influx into cells was measured and GPR41-mediated signaling by AR420626 was examined. An oral glucose tolerance test was performed, and plasma insulin levels were measured in streptozotocin-treated or high-fat diet-fed diabetic mice. The glycogen content was measured in skeletal muscle tissue. Results AR420626 increased basal and insulin-stimulated glucose uptake, which was reduced by pertussis toxin, an inhibitor of Gαi-mediated signaling, and treatment with small interfering RNA for GPR41 (siGPR41). AR420626 increased intracellular Ca2+ influx and phosphorylated Ca2+/calmodulin-dependent protein kinase type II, cyclic AMP-responsive element-binding protein, and mitogen-activated protein kinase (p38) in C2C12 myotubes, which were inhibited by treating with pertussis toxin, amlodipine (Ca2+ channel blocker), and siGPR41. AR420626 increased plasma insulin levels and skeletal muscle glycogen content and improved glucose tolerance in streptozotocin- and high-fat diet-induced diabetic mouse models. Conclusions GPR41 activation with AR420626 increased glucose uptake mediated by Ca2+ signaling via GPR41, improving diabetes mellitus." @default.
• W4380423149 created "2023-06-14" @default.
• W4380423149 creator A5004729487 @default.
• W4380423149 creator A5018392084 @default.
• W4380423149 creator A5062377822 @default.
• W4380423149 date "2023-06-13" @default.
• W4380423149 modified "2023-09-24" @default.
• W4380423149 title "Gα_i‐coupled <scp>GPR41</scp> activation increases Ca²⁺ influx in <scp>C2C12</scp> cells and shows a therapeutic effect in diabetic animals" @default.
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• W4380423149 doi "https://doi.org/10.1002/oby.23786" @default.
• W4380423149 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37309717" @default.
• W4380423149 hasPublicationYear "2023" @default.
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