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.