title: Postponing the Hypoglycemic Response to Partial Hepatectomy Delays Mouse Liver Regeneration.
abstract: All serious liver injuries alter metabolism and initiate hepatic regeneration. Recent studies using partial hepatectomy (PH) and other experimental models of liver regeneration implicate the metabolic response to hepatic insufficiency as an important source of signals that promote regeneration. Based on these considerations, the analyses reported here were undertaken to assess the impact of interrupting the hypoglycemic response to PH on liver regeneration in mice. A regimen of parenteral dextrose infusion that delays PH-induced hypoglycemia for 14 hours after surgery was identified, and the hepatic regenerative response to PH was compared between dextrose-treated and control mice. The results showed that regenerative recovery of the liver was postponed in dextrose-infused mice (versus vehicle control) by an interval of time comparable to the delay in onset of PH-induced hypoglycemia. The regulation of specific liver regeneration-promoting signals, including hepatic induction of cyclin D1 and S-phase kinase-associated protein 2 expression and suppression of peroxisome proliferator-activated receptor γ and p27 expression, was also disrupted by dextrose infusion. These data support the hypothesis that alterations in metabolism that occur in response to hepatic insufficiency promote liver regeneration, and they define specific pro- and antiregenerative molecular targets whose regenerative regulation is postponed when PH-induced hypoglycemia is delayed.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Schriefer
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Cliften
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Dennis
authors.initials: D
authors.lastname: Dietzen
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Sakil
authors.initials: S
authors.lastname: Kulkarni
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Sucha
authors.initials: S
authors.lastname: Sing
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Satdarshan P S
authors.initials: SP
authors.lastname: Monga
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri; Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri. Electronic address: rudnick_d@kids.wustl.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Rudnick
mesh_terms: D000818:Animals; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000008:administration & dosage*; D006498:Hepatectomy / Q000009:adverse effects; D048550:Hepatic Insufficiency / Q000517:prevention & control*; D006863:Hydrogen-Ion Concentration; D007003:Hypoglycemia / Q000188:drug therapy* / Q000209:etiology; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C530105:Ccnd1 protein, mouse; D047495:PPAR gamma; D044786:S-Phase Kinase-Associated Proteins; D019938:Cyclin D1; D005947:Glucose