HIF-1alpha is necessary to support gluconeogenesis during liver regeneration.
Coordinated recovery of hepatic glucose metabolism is prerequisite for normal liver regeneration. To examine roles of hypoxia inducible factor-1alpha (HIF-1alpha) 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 72h 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-1alpha in the regulation of gluconeogenesis under liver regeneration.
Tajima
Toshihide
T
Department of Obstetrics & Gynecology, Keio University, Shinjuku-ku, Tokyo, Japan.
Goda
Nobuhito
N
Fujiki
Natsuko
N
Hishiki
Takako
T
Nishiyama
Yasumasa
Y
Senoo-Matsuda
Nanami
N
Shimazu
Motohide
M
Soga
Tomoyoshi
T
Yoshimura
Yasunori
Y
Johnson
Randall S
RS
Suematsu
Makoto
M
D000818:Animals; D001786:Blood Glucose / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D005943:Gluconeogenesis / Q000235:genetics*; D006003:Glycogen / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008115:Liver Regeneration / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains
D001786:Blood Glucose; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D006003:Glycogen