Jejunal leptin-PI3K signaling lowers glucose production

Cell Metabolism
Brittany A RasmussenTony K T Lam

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.

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Citations

Sep 28, 2014·Molecular and Cellular Endocrinology·Frank A Duca, Jessica T Y Yue
Oct 7, 2015·Frontiers in Cellular Neuroscience·Stéphanie SeguraEmmanuel Moyse
Dec 3, 2015·Current Obesity Reports·Saurav ChakravarttyFrancesco Rubino
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Mar 1, 2014·The Journal of Biological Chemistry·Clémence D CôtéTony K T Lam
May 23, 2019·International Journal of Molecular Medicine·Fan YangLong Yang
Feb 25, 2014·Aging·Beatrice M Filippi, Tony K T Lam
Jul 16, 2016·The American Journal of Pathology·Shujun JiangXiang Gao

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