Glycogenesis and glucose oxidation during an intravenous glucose tolerance test in man

Abstract

The quantity of deuterated glucose customarily given in labelled IVGTTs (intravenous glucose tolerance tests) changes the isotopic composition of the subject's body water enough to be detected by mass spectrometric techniques. Glucose undergoing direct glycogenesis does not contribute label to the body water pool, and isotope incorporated into it must have come from glucose that has either been oxidized or undergone indirect glycogenesis. By subtracting the amount of label found in body water from the total amount of glucose utilized, as calculated from the minimal model of glucose disappearance, it should be possible to study the partitioning of the dose given between direct glycogenesis in skeletal muscle and other metabolic pathways. To establish these principles, we used isotope ratio MS to determine body water composition in groups of healthy (n=7; mean weight, 76 kg; fasting plasma glucose and insulin, 5.1 mmol and 40 pmol respectively) and Type II diabetic (n=5; mean weight, 84 kg; fasting plasma glucose and insulin, 6.2 mmol and 75 pmol respectively) subjects undergoing IVGTTs. It was found that, for healthy subjects, 31% of the dose given was utilized in direct glycogenesis and this was decreased to 15% in diabetes. Defects in muscle glycogen synthesis in diabetes of the same order are well known from magnetic resonance studies. We conclude that measurement of label incorporation into body water is potentially useful for investigation of the metabolism of a glucose load in vivo during an IVGTT.