@article{299cf2d419694877918d7ff672160bd3,
title = "Central GLP-2 enhances hepatic insulin sensitivity via activating PI3K signaling in POMC neurons",
abstract = "Summary Glucagon-like peptides (GLP-1/GLP-2) are coproduced and highlighted as key modulators to improve glucose homeostasis and insulin sensitivity after bariatric surgery. However, it is unknown if CNS GLP-2 plays any physiological role in the control of glucose homeostasis and insulin sensitivity. We show that mice lacking GLP-2 receptor (GLP-2R) in POMC neurons display glucose intolerance and hepatic insulin resistance. GLP-2R activation in POMC neurons is required for GLP-2 to enhance insulin-mediated suppression of hepatic glucose production (HGP) and gluconeogenesis. GLP-2 directly modulates excitability of POMC neurons in GLP-2R- and PI3K-dependent manners. GLP-2 initiates GLP-2R-p85α interaction and facilitates PI3K-Akt-dependent FoxO1 nuclear exclusion in POMC neurons. Central GLP-2 suppresses basal HGP and enhances insulin sensitivity, which are abolished in POMC-p110α KO mice. Thus, CNS GLP-2 plays a key physiological role in the control of HGP through activating PI3K-dependent modulation of membrane excitability and nuclear transcription of POMC neurons in the brain.",
author = "Xuemei Shi and Fuguo Zhou and Xiaojie Li and Benny Chang and Depei Li and Yi Wang and Qingchun Tong and Yong Xu and Makoto Fukuda and Zhao, {Jean J.} and Defa Li and Burrin, {Douglas G.} and Lawrence Chan and Xinfu Guan",
note = "Funding Information: The authors thank Zhuo Yang, Maria Truong, Shixiang Wen, An Hong Nguyen, Jian Qi, Wei Wang, Guangchen Zhang, Shaji Chacko, Daniel Donaldson, Jerome Stubblefield, Fang Zou, Liangru Zhu, Qiang Tong, Darryl Hadsell, Marta Fiorotto, Juan Marini, and Dennis Bier at Baylor College of Medicine for scientific and technical support. We also thank Yuanzhong Xu at the University of Texas Health Science Center at Houston for technical support. This work is supported by the USDA CRIS 6250-51000-055, NIH grants DK075489 and DK084125, and the National Natural Science Foundation of China Grant 30728016 (X.G.) and by NIH P30DK079638 (L.C.). X.S. and X.G. contributed to the study concept and design, acquisition of data, statistical analysis, interpretation of data, and drafting the manuscript. In addition, X.G. obtained funding, supervised the study, and finalized the manuscript. X.L. and B.C. contributed to the design and generation of the Glp2r floxed mice. F.Z., Y.W., Q.T., and Depei Li assisted with cell culture, in situ hybridization, and electrophysiological recording. Y.X., M.F., J.J.Z., Defa Li, D.G.B., and L.C. provided technical support and critically reviewed the manuscript. ",
year = "2013",
month = jul,
day = "2",
doi = "10.1016/j.cmet.2013.06.014",
language = "English (US)",
volume = "18",
pages = "86--98",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",
}