Tracer‐Based Estimates of Carbohydrate Homeostasis: Plasma and Tissue‐Specific Flux Glucose Indexing

Quantifying glucose production and glycogen flux, especially during a glucose challenge, should inform on the underlying nature of glucose intolerance and therein support therapeutic programs aimed at improving the regulation of blood glucose. Unfortunately, studies of glucose flux under conditions of a metabolic non‐steady state have proven difficult; although temporal changes in glucose concentration reflect the difference between the rates of input and output, quantification of specific rates has proved challenging. We aimed to determine the suitability of methods for phenotyping glucose homeostasis in rodents. First, we found that the oxidation of [6,6‐2H]glucose, normalized for insulin, yields data which are consistent with expected insulin resistance phenotypes. However, this method does not yield information regarding the contribution of specific tissues and/or pathways to the observed phenotype and simple non‐tracer based measures of glucose and insulin yield equivalent insight. Second, we were able to quantify tissue‐specific glucose uptake using a combination of 2‐deoxyglucose and mass‐balance methods during a glucose tolerance test; combining this with measures of the temporal change of plasma glucose labeling therein allows one to infer a glucose flux index, i.e. the relative suppression of endogenous glucose production and the tissue‐specific uptake. Last, we demonstrate hepatic glycogen cycling in rodents suggesting an important biochemical trait of glucose metabolism which translates between rodents and humans.