D-glucose metabolism displays anomeric specificity in pancreatic islets and other cell types. Recent studies have extended this knowledge to the effect of D-glucose to augment D-fructose phosphorylation by glucokinase in both pancreatic islet B-cells and hepatocytes, and have documented that the anomeric specificity of D-glucose metabolism in pancreatic islets implies enzyme-to-enzyme tunnelling of metabolites in the early steps of glycolysis. It is proposed that the anomeric specificity of D-glucose metabolism is essential to a sound understanding of carbohydrate homeostasis in health and disease.