Phosphatidyl inositol 3-kinase signaling in hypothalamic proopiomelanocortin neurons contributes to the regulation of glucose homeostasis

Jennifer W. Hill, Yong Xu, Frederic Preitner, Makota Fukuda, You Ree Cho, Ji Luo, Nina Balthasar, Roberto Coppari, Lewis C. Cantley, Barbara B. Kahn, Jean J. Zhao, Joel K. Elmquist

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Recent studies demonstrated a role for hypothalamic insulin and leptin action in the regulation of glucose homeostasis. This regulation involves proopiomelanocortin (POMC) neurons because suppression of phosphatidyl inositol 3-kinase (PI3K) signaling in these neurons blunts the acute effects of insulin and leptin on POMC neuronal activity. In the current study, we investigated whether disruption of PI3K signaling in POMC neurons alters normal glucose homeostasis using mouse models designed to both increase and decrease PI3K-mediated signaling in these neurons. We found that deleting p85α alone induced resistance to diet-induced obesity. In contrast, deletion of the p110α catalytic subunit of PI3K led to increased weight gain and adipose tissue along with reduced energy expenditure. Independent of these effects, increased PI3K activity in POMC neurons improved insulin sensitivity, whereas decreased PI3K signaling resulted in impaired glucose regulation. These studies show that activity of the PI3K pathway in POMC neurons is involved in not only normal energy regulation but also glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)4874-4882
Number of pages9
JournalEndocrinology
Volume150
Issue number11
DOIs
StatePublished - Nov 2009

ASJC Scopus subject areas

  • Endocrinology

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