Glucose effectiveness: Lessons from studies on insulin-independent glucose clearance in mice

Besides insulin-mediated transport of glucose into the cells, an important role is also played by the non-insulin-mediated transport. This latter process is called glucose effectiveness (acronym S_G ), which is estimated by modeling of glucose and insulin data after an intravenous glucose administration, and accounts for ≈70% of glucose disposal. This review summarizes studies on S_G , mainly in humans and rodents with focus on results achieved in model experiments in mice. In humans, S_G is reduced in type 2 diabetes, in obesity, in liver cirrhosis and in some elderly populations. In model experiments in mice, S_G is independent from glucose levels, but increases when insulin secretion is stimulated, such as after administration of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. S_G is reduced in insulin resistance induced by high-fat feeding and by exogenous administration of glucagon. Glucose-dependent (insulin-independent) glucose disposal is therefore important for glucose elimination, and it is also well regulated. It might be of pathophysiological relevance for the development of type 2 diabetes, in particular during insulin resistance, and might also be a target for glucose-reducing therapy. Measuring S_G is essentially important when carrying out metabolic studies to understand glucose homeostasis.