Year: 2008
Type: article
Abstract: The PI3K-Akt-FoxO1 pathway contributes to the actions of insulin and leptin in several cell types, including neurons in the CNS. However, identifying these actions in chemically identified neurons has proven difficult. To address this problem, we have developed a reporter mouse for monitoring PI3K-Akt signaling in specific populations of neurons, based on FoxO1 nucleocytoplasmic shuttling. The reporter, FoxO1 fused to green fluorescent protein (FoxO1GFP), is expressed under the control of a ubiquitous promoter that is silenced by a loxP flanked transcriptional blocker. Thus, the expression of the reporter in selected cells is dependent on the action of Cre recombinase. Using this model, we found that insulin treatment resulted in the nuclear exclusion of FoxO1GFP within POMC and AgRP neurons in a dose- and time-dependent manner. FoxO1GFP nuclear exclusion was also observed in POMC neurons following in vivo administration of insulin. In addition, leptin induced transient nuclear export of FoxO1GFP in POMC neurons in a dose dependent manner. Finally, insulin-induced nuclear export was impaired in POMC neurons by pretreatment with free fatty acids, a paradigm known to induce insulin resistance in peripheral insulin target tissues. Thus, our FoxO1GFP mouse provides a tool for monitoring the status of PI3K-Akt signaling in a cell-specific manner under physiological and pathophysiological conditions.
Source: Journal of Neuroscience
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: G1479954150, Central Mechanisms Regulating Energy Homeostasis, Project 2 of 10, Role of ghrelin in the counterregulatory response to insulin-induced hypoglycemia, Peripheral and Central Interactions in Energy Balance, Leptin Action and Central Melanocortin Systems, G3737249071, CNS Pathways Regulating Ghrelin Effects on Body Weight, G4556561717, Leptin Action and Central Melanocortin Systems, Interactions of Leptin and Central Serotonin Systems, G6673728491, G9000004678, G9000239758
OpenAlex ID: W2052806277