The pancreatic β-cell recognition of insulin secretagogues. Comparisons of glucose with glyceraldehyde isomers and dihydroxyacetone

d-Glyceraldehyde stimulated the release of insulin from pancreatic islets of Umeå- ob ob-mice whether or not glucose was present in the medium. Like the action of glucose, that of d-glyceraldehyde was biphasic in time, exhibited a sigmoidal dose-response relationship, was potentiated by theophylline, arginine, iodoacetamide, or l-glyceraldehyde, and was inhibited by epinephrine, 2,4-dinitrophenol, or Ca²⁺ deficiency. Half-maximum and maximum stimulations were produced by about 3 mm and 10 mm d-glyceraldehyde. Positive interactions were observed between 5 mm d-glyceraldehyde and 5 mm glucose and between 10 mm d-glyceraldehyde and 10 mm leucine. Mannoheptulose (10 mm) or glucosamine (10 mm) did not inhibit but potentiated the effect of 10 mm d-glyceraldehyde. Dihydroxyacetone (2.5-20 mm) also initiated insulin release in the absence of glucose. On the other hand, 5-10 mm l-glyceraldehyde did not initiate secretion but potentiated the effects of 5 mm glucose or 5 mm d-glyceraldehyde. d-Glyceraldehyde or dihydroxyacetone reduced the production of ¹⁴CO₂ from d-[U-¹⁴C]glucose; l-glyceraldehyde had a smaller and statistically insignificant effect. The results suggest that by being phosphorylated and entering glycolysis in the β-cells, d-glyceraldehyde and dihydroxyacetone act as functional analogues of glucose as secretory stimulus. Initiation of insulin release by glucose, d-glyceraldehyde, or dihydroxyacetone may thus depend on the production of a metabolic signal at or below the triose phosphate level.