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Determination of a glucose-dependent futile recycling rate constant from an intraperitoneal glucose tolerance test.

Abstract
Increased glucose cycling between glucose and glucose-6-phosphate is characteristic of insulin resistance and hyperglycemia seen with Type II diabetes. Traditionally, glucose cycling is determined by the difference between hepatic glucose output measured with separate [2-3H]glucose and [6-3H]glucose infusions. We demonstrate a novel method for determining hepatic glucose recycling from an intraperitoneal glucose tolerance test (IPGTT). A single tracer, [1, 2-13C(2)]glucose (a M2 glucose isotopomer), was administered at 1mg/g body weight to 4-month-old C57BL/6 mice. Hepatic glucose recycling was monitored by the appearance of a plasma M1 isotopomer of glucose, which is produced by the action of the pentose cycle on the M2 glucose isotopomer in the liver. The initial M2 enrichment was 56% and decreased to 13% at the end of 3 h, and the M1 enrichment peaked at 2 h. The ratio of plasma M1/M2 glucose increased linearly with time to approximately 25%, and the regression of the M1/M2 ratio against time gives a slope, termed the in vivo glucose-dependent futile recycling rate constant k(HR). k(HR) estimates glucose/glucose-6-phosphate futile cycling, along with glucose recycling through the pentose cycle. These observations demonstrate complex substrate cycling during an IPGTT using a single stable isotope tracer.
AuthorsJun Xu, W N Paul Lee, Gary Xiao, Chuck Trujillo, Vicky Chang, Lilia Blanco, Felicia Hernandez, Beau Chung, Sahar Makabi, Sayed Ahmed, Sara Bassilian, Mohammed Saad, Irwin J Kurland
JournalAnalytical biochemistry (Anal Biochem) Vol. 315 Issue 2 Pg. 238-46 (Apr 15 2003) ISSN: 0003-2697 [Print] United States
PMID12689833 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
CopyrightCopyright 2003 Elsevier Science (USA)
Chemical References
  • Blood Glucose
  • Carbon Isotopes
  • Insulin
  • Glycogen
  • Glucose
Topics
  • Animals
  • Blood Glucose (analysis)
  • Blotting, Western
  • Carbon Isotopes
  • Gas Chromatography-Mass Spectrometry
  • Glucose (administration & dosage, metabolism)
  • Glucose Tolerance Test
  • Glycogen (metabolism)
  • Glycolysis
  • Injections, Intraperitoneal
  • Insulin (blood, metabolism)
  • Isotope Labeling
  • Kinetics
  • Liver (metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Time Factors

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