Application of Isotopic Techniques Using Constant Specific Activity or Enrichment to the Study of Carbohydrate Metabolism

Abstract

Tracer techniques have become an established part of metabolic research and indeed are a fundamental part of our understanding of carbohydrate metabolism in humans. This review is meant to provide a basic overview of the problems and potential pitfalls associated with these techniques in the hope that they are reliably applied to newer areas of research. A quantitative measurement of the substrate fluxes that determine fasting or postprandial glucose concentrations is central to the determination of the pathophysiology of disease states and of measuring the effect of therapeutic interventions on the disease state. During the fasting state, glucose concentrations are dependent on the rate of endogenous glucose production (EGP) relative to the rate of glucose disappearance; measurement using tracer techniques is quite straightforward. The situation is more complex in the postprandial state, where gastric emptying, glucose absorption, the net sum of splanchnic extraction of ingested glucose (and therefore the rate of systemic appearance of ingested glucose), EGP, and glucose disappearance determine postprandial glucose concentrations (1,2). The tracer-based methodologies used to measure these fluxes, and their potential pitfalls, will be discussed. ### Tracers: stable vs. radioisotopes. The use of a substance (tracer) that can be used to follow a naturally occurring substrate (tracee) requires that such a substance experience the identical metabolic fate as the tracee. The ideal tracer can be detected with such precision as to require administration in trace amounts, thereby avoiding any alteration in the metabolism of the tracee (3). Tracers used for the purpose of metabolic research in humans are usually identical to the tracee, except that one or more atoms differ from the more abundant naturally occurring form of that atom. Such isotopes are radioactive when they spontaneously disintegrate to form another element, releasing radiation as a by-product of the decay. For example, 3H, which has one proton …