| First Author | Shi X | Year | 2013 |
| Journal | Cell Metab | Volume | 18 |
| Issue | 1 | Pages | 86-98 |
| PubMed ID | 23823479 | Mgi Jnum | J:199234 |
| Mgi Id | MGI:5501356 | Doi | 10.1016/j.cmet.2013.06.014 |
| Citation | Shi X, et al. (2013) Central GLP-2 Enhances Hepatic Insulin Sensitivity via Activating PI3K Signaling in POMC Neurons. Cell Metab 18(1):86-98 |
| abstractText | 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-p85alpha 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-p110alpha 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. |
