Hepatic insulin signalling is dispensable for suppression of glucose output by insulin in vivo

Paul M. Titchenell, Qingwei Chu, Bobby R. Monks and Morris J. Birnbaum ()
Additional contact information
Paul M. Titchenell: Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania
Qingwei Chu: Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania
Bobby R. Monks: Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania
Morris J. Birnbaum: Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: Abstract Insulin signalling and nutrient levels coordinate the metabolic response to feeding in the liver. Insulin signals in hepatocytes to activate Akt, which inhibits Foxo1 suppressing hepatic glucose production (HGP) and allowing the transition to the postprandial state. Here we provide genetic evidence that insulin regulates HGP by both direct and indirect hepatic mechanisms. Liver-specific ablation of the IR (L-Insulin Receptor KO) induces glucose intolerance, insulin resistance and prevents the appropriate transcriptional response to feeding. Liver-specific deletion of Foxo1 (L-IRFoxo1DKO) rescues glucose tolerance and allows for normal suppression of HGP and gluconeogenic gene expression in response to insulin, despite lack of autonomous liver insulin signalling. These data indicate that in the absence of Foxo1, insulin signals via an intermediary extrahepatic tissue to regulate liver glucose production. Importantly, a hepatic mechanism distinct from the IR–Akt–Foxo1 axis exists to regulate glucose production.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms8078 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8078

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms8078

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().