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HIF-1α is necessary to support gluconeogenesis during liver regeneration

Authors
  • Tajima, Toshihide
  • Goda, Nobuhito
  • Fujiki, Natsuko
  • Hishiki, Takako
  • Nishiyama, Yasumasa
  • Senoo-Matsuda, Nanami
  • Shimazu, Motohide
  • Soga, Tomoyoshi
  • Yoshimura, Yasunori
  • Johnson, Randall S.
  • Suematsu, Makoto
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
Publication Date
Jan 01, 2009
Volume
387
Issue
4
Pages
789–794
Identifiers
DOI: 10.1016/j.bbrc.2009.07.115
Source
Elsevier
Keywords
License
Unknown

Abstract

Coordinated recovery of hepatic glucose metabolism is prerequisite for normal liver regeneration. To examine roles of hypoxia inducible factor-1α (HIF-1α) for hepatic glucose homeostasis during the reparative process, we inactivated the gene in hepatocytes in vivo. Following partial hepatectomy (PH), recovery of residual liver weight was initially retarded in the mutant mice by down-regulation of hepatocyte proliferation, but occurred comparably between the mutant and control mice at 72 h after PH. At this time point, the mutant mice showed lowered blood glucose levels with enhanced accumulation of glycogen in the liver. The mutant mice exhibited impairment of hepatic gluconeogenesis as assessed by alanine tolerance test. This appeared to result from reduced expression of PGK-1 and PEPCK since 3-PG, PEP and malate were accumulated to greater extents in the regenerated liver. In conclusion, these findings provide evidence for roles of HIF-1α in the regulation of gluconeogenesis under liver regeneration.

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