Metabolic and insulin-releasing activities of D-glucose anomers

Abstract

GRODSKY et al.¹ proposed that glucose stimulates insulin secretion because the sugar is metabolised in the pancreatic β cells; this view of stimulus recognition was later termed the substrate–site hypothesis². The hypothesis has received support from observed correlations between rates of insulin release and various parameters of glucose metabolism in the pancreatic islets. It is particularly striking that a triose, D-glyceraldehyde, has been shown to mimic the electrophysiological³ and insulin-releasing^4–6 actions of glucose; D-glyceraldehyde is oxidised and dilutes ¹⁴CO₂ arising from D-(U-¹⁴C)-glucose in the islets^4–6. Although the substrate–site hypothesis has been criticised (for example, refs 7 and 8), many of the arguments raised may be doubtful for reasons discussed elsewhere⁹. An important challenge to the hypothesis is the observation that the α anomer of D-glucose is more effective than the β anomer in stimulating insulin secretion^10,11. For the anomeric specificity of the D-glucose recognition system to stand up as evidence against the substrate–site hypothesis, however, it must be shown that the transport, phosphorylation or further metabolism of glucose does not exhibit the same anomeric specificity in the β cell. We report here that β-D-glucose is at least as effective as α-D-glucose in stimulating counter-transport of 3-O-methyl-D-glucose, increasing the islet content of glucose-6-phosphate, and diluting ³H₂O that results from the metabolism of D-(5-³H)-glucose.