Cytosolic phosphoenolpyruvate carboxykinase as a cataplerotic pathway in the small intestine

Austin Potts, Aki Uchida, Stanislaw Deja, Eric D. Berglund, Blanka Kucejova, Joao A. Duarte, Xiaorong Fu, Jeffrey D. Browning, Mark A. Magnuson, Shawn C. Burgess

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Cytosolic phosphoenolpyruvate carboxykinase (PEPCK) is a gluconeogenic enzyme that is highly expressed in the liver and kidney but is also expressed at lower levels in a variety of other tissues where it may play adjunct roles in fatty acid esterification, amino acid metabolism, and/or TCA cycle function. PEPCK is expressed in the enterocytes of the small intestine, but it is unclear whether it supports a gluconeogenic rate sufficient to affect glucose homeostasis. To examine potential roles of intestinal PEPCK, we generated an intestinal PEPCK knockout mouse. Deletion of intestinal PEPCK ablated ex vivo gluconeogenesis but did not significantly affect glycemia in chow, high-fat diet, or streptozotocin-treated mice. In contrast, postprandial triglyceride secretion from the intestine was attenuated in vivo, consistent with a role in fatty acid esterification. Intestinal amino acid profiles and13C tracer appearance into these pools were significantly altered, indicating abnormal amino acid trafficking through the enterocyte. The data suggest that the predominant role of PEPCK in the small intestine of mice is not gluconeogenesis but rather to support nutrient processing, particularly with regard to lipids and amino acids. NEW & NOTEWORTHY The small intestine expresses gluconeogenic enzymes for unknown reasons. In addition to glucose synthesis, the nascent steps of this pathway can be used to support amino acid and lipid metabolisms. When phosphoenolpyruvate carboxykinase, an essential gluconeogenic enzyme, is knocked out of the small intestine of mice, glycemia is unaffected, but mice inefficiently absorb dietary lipid, have abnormal amino acid profiles, and inefficiently catabolize glutamine. Therefore, the initial steps of intestinal gluconeogenesis are used for processing dietary triglycerides and metabolizing amino acids but are not essential for maintaining blood glucose levels.

Original languageEnglish (US)
Pages (from-to)G249-G258
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume315
Issue number2
DOIs
StatePublished - Aug 3 2018

Fingerprint

Phosphoenolpyruvate
Small Intestine
Amino Acids
Gluconeogenesis
Enterocytes
Esterification
Triglycerides
Enzymes
Fatty Acids
Lipids
Glucose
Essential Amino Acids
High Fat Diet
Streptozocin
Glutamine
Lipid Metabolism
Knockout Mice
Intestines
Blood Glucose
Homeostasis

Keywords

  • Amino acids
  • Cataplerosis
  • Gluconeogenesis
  • Glyceroneogenesis
  • Small intestine

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Cytosolic phosphoenolpyruvate carboxykinase as a cataplerotic pathway in the small intestine. / Potts, Austin; Uchida, Aki; Deja, Stanislaw; Berglund, Eric D.; Kucejova, Blanka; Duarte, Joao A.; Fu, Xiaorong; Browning, Jeffrey D.; Magnuson, Mark A.; Burgess, Shawn C.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 315, No. 2, 03.08.2018, p. G249-G258.

Research output: Contribution to journalArticle

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AU - Duarte, Joao A.

AU - Fu, Xiaorong

AU - Browning, Jeffrey D.

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