Linked Life Data

12176975

Source:http://linkedlifedata.com/resource/pubmed/id/12176975

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2002-12-23
pubmed:abstractText
The hypoglycemia seen in the fasting PPARalpha null mouse is thought to be due to impaired liver fatty acid beta-oxidation. The etiology of hypoglycemia in the PPARalpha null mouse was determined via stable isotope studies. Glucose, lactate, and glycerol flux was assessed in the fasted and fed states in 4-month-old PPARalpha null mice and in C57BL/6 WT maintained on standard chow using a new protocol for flux assessment in the fasted and fed states. Hepatic glucose production (HGP) and glucose carbon recycling were estimated using [U-(13)C(6)]glucose, and HGP, lactate, and glycerol turnover was estimated utilizing either [U-(13)C(3)]lactate or [2-(13)C]glycerol infused subcutaneously via Alza miniosmotic pumps. At the end of a 17-h fast, HGP was higher in the PPARalpha null mice than in WT by 37% (p < 0.01). However, recycling of glucose carbon from lactate back to glucose was lower in the PPARalpha null than in WT (39% versus 51%, p < 0.02). The lack of conversion of lactate to glucose was confirmed using an [U-(13)C(3)]lactate infusion. In the fasted state, HGP from lactate and lactate production were decreased by 65 and 55%, respectively (p < 0.05) in PPARalpha null mice. In contrast, when [2-(13)C]glycerol was infused, glycerol production and HGP from glycerol increased by 80 and 250%, respectively (p < 0.01), in the fasted state of PPARalpha null mice. The increased HGP from glycerol was not suppressed in the fed state. While little change was evident for phosphoenolpyruvate carboxykinase (PEPCK) expression, pyruvate kinase expression was decreased 16-fold in fasted PPARalpha null mice as compared with the wild-type control. The fasted and fed insulin levels were comparable, but blood glucose levels were lower in the PPARalpha null mice than in controls. In conclusion, PPARalpha receptor function creates a setpoint for a metabolic network that regulates the rate and route of HGP in the fasted and fed states, in part, by controlling the flux of glycerol and lactate between the triose-phosphate and pyruvate/lactate pools.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
50237-44
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12176975-Animals, pubmed-meshheading:12176975-Base Sequence, pubmed-meshheading:12176975-Blood Glucose, pubmed-meshheading:12176975-Carbon Isotopes, pubmed-meshheading:12176975-DNA Primers, pubmed-meshheading:12176975-Fasting, pubmed-meshheading:12176975-Gene Expression Regulation, Enzymologic, pubmed-meshheading:12176975-Gluconeogenesis, pubmed-meshheading:12176975-Glucose, pubmed-meshheading:12176975-Glycerol, pubmed-meshheading:12176975-Homeostasis, pubmed-meshheading:12176975-Insulin, pubmed-meshheading:12176975-Lactic Acid, pubmed-meshheading:12176975-Liver, pubmed-meshheading:12176975-Mice, pubmed-meshheading:12176975-Mice, Inbred C57BL, pubmed-meshheading:12176975-Mice, Knockout, pubmed-meshheading:12176975-Models, Biological, pubmed-meshheading:12176975-Phosphoenolpyruvate Carboxykinase (GTP), pubmed-meshheading:12176975-Pyruvate Kinase, pubmed-meshheading:12176975-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:12176975-Transcription Factors
pubmed:year
2002
pubmed:articleTitle
Peroxisome proliferator-activated receptor alpha (PPARalpha) influences substrate utilization for hepatic glucose production.
pubmed:affiliation
Department of Medicine, the Laboratory of Metabolomics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't