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

Abstract

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 Ca 2+ deficiency. Half-maximum and maximum stimulations were produced by about 3 m m and 10 m m d-glyceraldehyde. Positive interactions were observed between 5 m m d-glyceraldehyde and 5 m m glucose and between 10 m m d-glyceraldehyde and 10 m m leucine. Mannoheptulose (10 m m) or glucosamine (10 m m) did not inhibit but potentiated the effect of 10 m m d-glyceraldehyde. Dihydroxyacetone (2.5–20 m m) also initiated insulin release in the absence of glucose. On the other hand, 5–10 m m l-glyceraldehyde did not initiate secretion but potentiated the effects of 5 m m glucose or 5 m m d-glyceraldehyde. d-Glyceraldehyde or dihydroxyacetone reduced the production of 14CO 2 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.