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

Jun 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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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, 2-13C2]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 3h, and the M1 enrichment peaked at 2h. The ratio of plasma M1/M2 glucose increased linearly with time to ∼25%, and the regression of the M1/M2 ratio against time gives a slope, termed the in vivo glucose-dependent futile recycling rate constant kHR·kHR 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.

Original languageEnglish (US)
Pages (from-to)238-246
Number of pages9
JournalAnalytical Biochemistry
Volume315
Issue number2
DOIs
StatePublished - Apr 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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