| Zonation of gluconeogenesis, ketogenesis and intracellular pH in livers from normal and diabetic ketoacidotic rats: evidence for intralobular redistribution of metabolic events in ketoacidosis. | |
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MedLine Citation:
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PMID: 10493939 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The intralobular distribution of metabolism was examined in the livers from rats with severe diabetic ketoacidosis (DKA), perfused at pH 6.8, and compared with that in livers from normal starved animals perfused at either pH 7.4 or 6.8. With lactate and palmitate as substrates, the perivenous uptake of periportally synthesized glucose seen in normal livers at pH 7.4 was abolished during DKA; indeed, gluconeogenesis was most active in the perivenous region. Whereas in normal livers perfused at pH 7.4 the periportal region showed a markedly elevated intracellular pH (pH(i)) compared with the perivenous zone, this distribution of pH(i) was reversed in DKA, with an intermediate distribution in normal livers perfused at pH 6. 8. 3-Hydroxybutyrate was generated throughout the lobule. Some acetoacetate generated periportally was converted to 3-hydroxybutyrate more perivenously. A steep gradient of oxygen uptake along the radius of the lobule was apparent in all three groups; oxygen uptake was greatly decreased perivenously despite adequate oxygen supply. These findings are consistent with our previous observations of the lobular co-location of high pH(i) and gluconeogenesis, and might offer an explanation of how high gluconeogenic rates can continue in spite of severe systemic acidosis in DKA. The findings provide direct evidence for a marked redistribution of intralobular metabolism in DKA. |
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Authors:
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S P Burns; R D Cohen; R A Iles; R A Bailey; M Desai; J P Germain; T C Going |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 343 Pt 1 ISSN: 0264-6021 ISO Abbreviation: Biochem. J. Publication Date: 1999 Oct |
Date Detail:
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Created Date: 1999-12-07 Completed Date: 1999-12-07 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 273-80 Citation Subset: IM |
Affiliation:
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Medical Unit (Whitechapel), St Bartholomew's and the Royal London Hospital School of Medicine and Dentistry, London E1 1BB, U.K. s.p.burns@mds.qmw.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Diabetic Ketoacidosis / metabolism* Gluconeogenesis* Glucose / metabolism Hydrogen-Ion Concentration* Ketone Bodies / biosynthesis* Liver / metabolism* Magnetic Resonance Spectroscopy Male Oxygen Consumption Rats Rats, Wistar |
| Grant Support | |
ID/Acronym/Agency:
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//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Ketone Bodies; 50-99-7/Glucose |
| Comments/Corrections | |
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