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Cell Metab. 2014 Jan 7;19(1):155-61. doi: 10.1016/j.cmet.2013.11.014. Epub 2013 Dec 19.

Jejunal leptin-PI3K signaling lowers glucose production.

Author information

1
Toronto General Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
2
Toronto General Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
3
Toronto General Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Banting and Best Diabetes Centre, University of Toronto, Toronto, ON M5G 2C4, Canada. Electronic address: tony.lam@uhnres.utoronto.ca.

Erratum in

  • Cell Metab. 2014 Mar 4;19(3):548.

Abstract

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.

PMID:
24361011
DOI:
10.1016/j.cmet.2013.11.014
[Indexed for MEDLINE]
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