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Publication : PI3K integrates the action of insulin and leptin on hypothalamic neurons.

First Author  Xu AW Year  2005
Journal  J Clin Invest Volume  115
Issue  4 Pages  951-8
PubMed ID  15761497 Mgi Jnum  J:97407
Mgi Id  MGI:3575379 Doi  10.1172/JCI24301
Citation  Xu AW, et al. (2005) PI3K integrates the action of insulin and leptin on hypothalamic neurons. J Clin Invest 115(4):951-958
abstractText  Central control of energy balance depends on the ability of proopiomelanocortin (POMC) or agouti-related protein (Agrp) hypothalamic neurons to sense and respond to changes in peripheral energy stores. Leptin and insulin have been implicated as circulating indicators of adiposity, but it is not clear how changes in their levels are perceived or integrated by individual neuronal subtypes. We developed mice in which a fluorescent reporter for PI3K activity is targeted to either Agrp or POMC neurons and used 2-photon microscopy to measure dynamic regulation of PI3K by insulin and leptin in brain slices. We show that leptin and insulin act in parallel to stimulate PI3K in POMC neurons but in opposite ways on Agrp neurons. These results suggest a new view of hypothalamic circuitry, in which the effects of leptin and insulin are integrated by anorexigenic but not by orexigenic neurons.
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