Jejunal leptin-PI3K signaling lowers glucose production

Brittany A. Rasmussen, Danna M. Breen, Frank A. Duca, Clémence D. Côté, Melika Zadeh Tahmasebi, Beatrice M. Filippi, Tony K.T. Lam

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


The fat-derived hormone leptin binds to its hypothalamic receptors to regulate glucose homeostasis. Leptin is also synthesized in the stomach and subsequently binds to its receptors expressed in the intestine, although the functional relevance of such activation remains largely unknown. We report here that intrajejunal leptin administration activates jejunal leptin receptors and signals through a phosphatidylinositol 3-kinase (PI3K)-dependent and signal transducer and activator of transcription 3 (STAT3)-independent signaling pathway to lower glucose production in healthy rodents. Jejunal leptin action is sufficient to lower glucose production in uncontrolled diabetic and high-fat-fed rodents and contributes to the early antidiabetic effect of duodenal-jejunal bypass surgery. These data unveil a glucoregulatory site of leptin action and suggest that enhancing leptin-PI3K signaling in the jejunum lowers plasma glucose concentrations in diabetes.

Original languageEnglish (US)
Pages (from-to)155-161
Number of pages7
JournalCell Metabolism
Issue number1
StatePublished - Jan 7 2014

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Jejunal leptin-PI3K signaling lowers glucose production'. Together they form a unique fingerprint.

Cite this