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Usage Information

PI3K integrates the action of insulin and leptin on hypothalamic neurons
Allison Wanting Xu, Christopher B. Kaelin, Kiyoshi Takeda, Shizuo Akira, Michael W. Schwartz, Gregory S. Barsh
Allison Wanting Xu, Christopher B. Kaelin, Kiyoshi Takeda, Shizuo Akira, Michael W. Schwartz, Gregory S. Barsh
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Article Metabolism

PI3K integrates the action of insulin and leptin on hypothalamic neurons

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Abstract

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.

Authors

Allison Wanting Xu, Christopher B. Kaelin, Kiyoshi Takeda, Shizuo Akira, Michael W. Schwartz, Gregory S. Barsh

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Usage data is cumulative from June 2025 through June 2026.

Usage JCI PMC
Text version 1,438 89
PDF 236 20
Figure 474 11
Table 101 0
Supplemental data 96 0
Citation downloads 175 0
Totals 2,520 120
Total Views 2,640
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