| First Author | Könner AC | Year | 2007 |
| Journal | Cell Metab | Volume | 5 |
| Issue | 6 | Pages | 438-49 |
| PubMed ID | 17550779 | Mgi Jnum | J:129853 |
| Mgi Id | MGI:3770317 | Doi | 10.1016/j.cmet.2007.05.004 |
| Citation | Konner AC, et al. (2007) Insulin Action in AgRP-Expressing Neurons Is Required for Suppression of Hepatic Glucose Production. Cell Metab 5(6):438-449 |
| abstractText | Insulin action in the central nervous system regulates energy homeostasis and glucose metabolism. To define the insulin-responsive neurons that mediate these effects, we generated mice with selective inactivation of the insulin receptor (IR) in either pro-opiomelanocortin (POMC)- or agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus. While neither POMC- nor AgRP-restricted IR knockout mice exhibited altered energy homeostasis, insulin failed to normally suppress hepatic glucose production during euglycemic-hyperinsulinemic clamps in AgRP-IR knockout (IR(DeltaAgRP)) mice. These mice also exhibited reduced insulin-stimulated hepatic interleukin-6 expression and increased hepatic expression of glucose-6-phosphatase. These results directly demonstrate that insulin action in POMC and AgRP cells is not required for steady-state regulation of food intake and body weight. However, insulin action specifically in AgRP-expressing neurons does play a critical role in controlling hepatic glucose production and may provide a target for the treatment of insulin resistance in type 2 diabetes. |
