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Publication
FoxO1 integrates direct and indirect effects of insulin on hepatic glucose
production and glucose utilization.
Authors O-Sullivan I, Zhang W, Wasserman DH, Liew CW, Liu J, Paik J, DePinho RA, Stolz
DB, Kahn CR, Schwartz MW, Unterman TG
Submitted By Terry Unterman on 7/24/2015
Status Published
Journal Nature communications
Year 2015
Date Published
Volume : Pages 6 : 7079
PubMed Reference 25963540
Abstract FoxO proteins are major targets of insulin action. To better define the role of
FoxO1 in mediating insulin effects in the liver, we generated liver-specific
insulin receptor knockout (LIRKO) and IR/FoxO1 double knockout (LIRFKO) mice.
Here we show that LIRKO mice are severely insulin resistant based on glucose,
insulin and C-peptide levels, and glucose and insulin tolerance tests, and
genetic deletion of hepatic FoxO1 reverses these effects. (13)C-glucose and
insulin clamp studies indicate that regulation of both hepatic glucose
production (HGP) and glucose utilization is impaired in LIRKO mice, and these
defects are also restored in LIRFKO mice corresponding to changes in gene
expression. We conclude that (1) inhibition of FoxO1 is critical for both direct
(hepatic) and indirect effects of insulin on HGP and utilization, and (2)
extrahepatic effects of insulin are sufficient to maintain normal whole-body and
hepatic glucose metabolism when liver FoxO1 activity is disrupted.






Genes
SymbolDescription
Foxo1forkhead box O1
Insrinsulin receptor

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