Determination of a glucose-dependent futile recycling rate constant from an intraperitoneal glucose tolerance test.
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.
Xu
Jun
J
Department of Medicine, University of California, Los Angeles, CA 90095, USA.
Lee
W N Paul
WN
Xiao
Gary
G
Trujillo
Chuck
C
Chang
Vicky
V
Blanco
Lilia
L
Hernandez
Felicia
F
Chung
Beau
B
Makabi
Sahar
S
Ahmed
Sayed
S
Bassilian
Sara
S
Saad
Mohammed
M
Kurland
Irwin J
IJ
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D002247:Carbon Isotopes; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007553:Isotope Labeling; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
D001786:Blood Glucose; D002247:Carbon Isotopes; D007328:Insulin; D006003:Glycogen; D005947:Glucose