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Gluconeogenesis Flux in Metabolic Disease

Annual Review of Nutrition
Vol. 43:153-177 (Volume publication date August 2023)
https://doi.org/10.1146/annurev-nutr-061121-091507 (https://doi.org/10.1146/annurev-nutr-061121-091507)

Ankit Shah and Fredric E. Wondisford

Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey, USA;
email: ashah386@rwjms.rutgers.edu (mailto:ashah386@rwjms.rutgers.edu), few11@rwjms.rutgers.edu
(mailto:few11@rwjms.rutgers.edu)

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Sections
ABSTRACT | KEYWORDS | INTRODUCTION (/DOI/FULL/10.1146/ANNUREV-NUTR-061121-091507#_I2) |
DISEASES ASSOCIATED WITH INSULIN RESISTANCE (/DOI/FULL/10.1146/ANNUREV-NUTR-061121-091507#_I8) |
HORMONAL IMBALANCES AFFECTING GLUCONEOGENESIS (/DOI/FULL/10.1146/ANNUREV-NUTR-061121-091507#_I12) |
INBORN ERRORS IN METABOLISM (/DOI/FULL/10.1146/ANNUREV-NUTR-061121-091507#_I19) |
ALTERED GLUCONEOGENIC ENZYME ACTIVITY IN CANCER (/DOI/FULL/10.1146/ANNUREV-NUTR-061121-091507#_I27) |
PERSPECTIVE AND FUTURE DIRECTIONS (/DOI/FULL/10.1146/ANNUREV-NUTR-061121-091507#_I30) | PDF
DISCLOSURE STATEMENT (/DOI/FULL/10.1146/ANNUREV-NUTR-061121-091507#_I31) |
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Abstract

Gluconeogenesis is a critical biosynthetic process that helps maintain whole-body glucose homeostasis and
becomes altered in certain medical diseases. We review gluconeogenic flux in various medical diseases,
including common metabolic disorders, hormonal imbalances, specific inborn genetic errors, and cancer.
We discuss how the altered gluconeogenic activity contributes to disease pathogenesis using data from
experiments using isotopic tracer and spectroscopy methodologies. These in vitro, animal, and human
studies provide insights into the changes in circulating levels of available gluconeogenesis substrates and
the efficiency of converting those substrates to glucose by gluconeogenic organs. We highlight ongoing
knowledge gaps, discuss emerging research areas, and suggest future investigations. A better understanding
of altered gluconeogenesis flux may ultimately identify novel and targeted treatment strategies for such
diseases.

Keywords

gluconeogenesis (/keyword/Gluconeogenesis), metabolic flux (/keyword/Metabolic+Flux), insulin resistance

(/keyword/Insulin+Resistance), hormones (/keyword/Hormones), enzyme deficiency
(/keyword/Enzyme+Deficiency), cancer (/keyword/Cancer)

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