title: PEPCK-C reexpression in the liver counters neonatal hypoglycemia in Pck1del/delmice, unmasking role in non-gluconeogenic tissues.
abstract: Whole body cytosolic phosphoenolpyruvate carboxykinase knockout (PEPCK-C KO) mice die early after birth with profound hypoglycemia therefore masking the role of PEPCK-C in adult, non-gluconeogenic tissues where it is expressed. To investigate whether PEPCK-C deletion in the liver was critically responsible for the hypoglycemic phenotype, we reexpress this enzyme in the liver of PEPCK-C KO pups by early postnatal administration of PEPCK-C-expressing adenovirus. This maneuver was sufficient to partially rescue hypoglycemia and allow the pups to survive and identifies the liver as a critical organ, and hypoglycemia as the critical pathomechanism, leading to early postnatal death in the whole-body PEPCK-C knockout mice. Pathology assessment of survivors also suggest a possible role for PEPCK-C in lung maturation and muscle metabolism.
authors: Department of Physiological Sciences, Faculty of Medicine, University of Barcelona, L'Hospitalet del Llobregat, Barcelona, Spain.
authors: Jana
authors: J
authors: Semakova
authors: Department of Physiological Sciences, Faculty of Medicine, University of Barcelona, L'Hospitalet del Llobregat, Barcelona, Spain.
authors: Petra
authors: P
authors: Hyroššová
authors: Department of Physiological Sciences, Faculty of Medicine, University of Barcelona, L'Hospitalet del Llobregat, Barcelona, Spain.
authors: Andrés
authors: A
authors: Méndez-Lucas
authors: Division of Pathology, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors: Ernest
authors: E
authors: Cutz
authors: Department of Physiological Sciences, Faculty of Medicine, University of Barcelona, L'Hospitalet del Llobregat, Barcelona, Spain.
authors: Jordi
authors: J
authors: Bermudez
authors: Advanced Imaging Research Center and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors: Shawn
authors: S
authors: Burgess
authors: Department of Experimental Pathology and Therapeutics, Faculty of Medicine, University of Barcelona, L'Hospitalet del Llobregat, Barcelona, Spain.
authors: Soledad
authors: S
authors: Alcántara
authors: Department of Physiological Sciences, Faculty of Medicine, University of Barcelona, L'Hospitalet del Llobregat, Barcelona, Spain. jperales@ub.edu.|IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain. jperales@ub.edu.
authors: José C
authors: JC
authors: Perales
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002239:Carbohydrate Metabolism, Inborn Errors / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy / Q000662:veterinary*; D003433:Crosses, Genetic; D018014:Gene Transfer Techniques; D005943:Gluconeogenesis; D006579:Heterozygote; D007003:Hypoglycemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D066292:Lipid Droplets / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D008064:Lipidoses / Q000209:etiology; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy / Q000662:veterinary*; D008168:Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D010729:Phosphoenolpyruvate Carboxykinase (GTP)
keywords: Gluconeogenesis; Hepatic lipidosis; KO; Liver; Neonatal hypoglycemia; PEPCK