Stimulus-secretion coupling of glucose-induced insulin release. Metabolism of alpha- and beta-D-glucose in isolated islets.
Alpha-D-Glucose is known to exert more marked insulinotropic action than B-D-glucose. Both anomers are phosphorylated at the same rate by rat islet homogenates. The islet glucose-6-phosphate dehydrogenase displays a preferential affinity towards beta-D-glucose-6-phosphate, and this coincides with a higher sorbitol content in the islets exposed to beta-D-glucose. On the contrary, the islet phosphoglucose isomerase is stereospecific for alpha-D-glucose 6-phosphate and, hence, the concentration of glucose 6-phosphate is lower and that of the alpha-anomer to lactate and CO2 is also higher than that of beta-D-glucose. This increased glycolytic flux is associated with a more marked inhibitory action on 14Ca efflux, a more pronounced stimulation of 45Ca net uptake and a higher rate of insulin release in the islets exposed to alpha-D-glucose. The more marked insulinotropic action of alpha- as a distinct from beta-D-glucose is thus compatible with the view that glycolysis represents the key component of the sensor device through which glucose is identified in the pancreatic B-cell as a stimulus for insulin release.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005958:Glucosephosphates / Q000378:metabolism; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism; D013237:Stereoisomerism
D005958:Glucosephosphates; D007328:Insulin; D007773:Lactates; D013012:Sorbitol; D005954:Glucosephosphate Dehydrogenase; D006593:Hexokinase; D005956:Glucose-6-Phosphate Isomerase; D005947:Glucose; D002118:Calcium