Insulin regulation of gluconeogenesis

Maximilian Hatting, Clint D.J. Tavares, Kfir Sharabi, Amy K. Rines, Pere Puigserver*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

329 Scopus citations

Abstract

The coordinated regulation between cellular glucose uptake and endogenous glucose production is indispensable for the maintenance of constant blood glucose concentrations. The liver contributes significantly to this process by altering the levels of hepatic glucose release, through controlling the processes of de novo glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis). Various nutritional and hormonal stimuli signal to alter hepatic gluconeogenic flux, and suppression of this metabolic pathway during the postprandial state can, to a significant extent, be attributed to insulin. Here, we review some of the molecular mechanisms through which insulin modulates hepatic gluconeogenesis, thus controlling glucose production by the liver to ultimately maintain normoglycemia. Various signaling pathways governed by insulin converge at the level of transcriptional regulation of the key hepatic gluconeogenic genes PCK1 and G6PC, highlighting this as one of the focal mechanisms through which gluconeogenesis is modulated. In individuals with compromised insulin signaling, such as insulin resistance in type 2 diabetes, insulin fails to suppress hepatic gluconeogenesis, even in the fed state; hence, an insight into these insulin-moderated pathways is critical for therapeutic purposes.

Original languageAmerican English
Pages (from-to)21-35
Number of pages15
JournalAnnals of the New York Academy of Sciences
Volume1411
Issue number1
DOIs
StatePublished - 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 New York Academy of Sciences.

Keywords

  • gluconeogenesis
  • glucose
  • glycogenolysis
  • insulin
  • regulation

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