HIF-1{alpha} is necessary to support gluconeogenesis during liver regeneration

Journal Article · Fri Oct 02 04:00:00 EDT 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2009.07.115· OSTI ID:22199819

Tajima, Toshihide ^[1]; Goda, Nobuhito ^[2]; Fujiki, Natsuko; Hishiki, Takako; Nishiyama, Yasumasa ^[3]; Senoo-Matsuda, Nanami ^[2]; Shimazu, Motohide ^[4]; Soga, Tomoyoshi ^[5]; Yoshimura, Yasunori ^[1]; Johnson, Randall S. ^[6]; Suematsu, Makoto ^[3]

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1. Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)
2. Department of Life Science and Medical Bio-Science, School of Advanced Science and Engineering, Waseda University, TWIns 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan)
3. Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)
4. Department of Surgery, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo 193-0998 (Japan)
5. The Institute for Advanced Biosciences, Keio University, Tsuruoka City, Yamagata 997-0052 (Japan)
6. Molecular Biology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093 (United States)

Coordinated recovery of hepatic glucose metabolism is prerequisite for normal liver regeneration. To examine roles of hypoxia inducible factor-1{alpha} (HIF-1{alpha}) 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-1{alpha} in the regulation of gluconeogenesis under liver regeneration.

• OSTI ID: 22199819
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 387; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALANINES
BLOOD
FRUCTOSE
GLUCOSE
GLYCOGEN
HEPATECTOMY
HOMEOSTASIS
LIVER
LIVER CELLS
MICE
MUTANTS
PHOSPHATES
PHOSPHOENOLPYRUVATE