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.