The changes in adenine nucleotides measured in glucose-stimulated rodent islets occur in beta cells but not in a cells and are also observed in humanislets

Glucose metabolism by pancreatic beta and alpha cells is essential for stim ulation of insulin secretion and inhibition of glucagon secretion. Studies using rodent islets have suggested that the ATP/ADP ratio serves as second messenger in beta cells. This study compared the effects of glucose on gluc ose oxidation ([U-C-14]glucose) and adenine nucleotides (luminometric metho d) in purified rat alpha and beta cells. The rate of glucose oxidation at 1 mM glucose was higher in beta than alpha cells (4.5-fold, i,e, similar to 2-fold after normalization for cell size). It was more strongly stimulated by 10 mM glucose in beta cells (9-fold) than in a cells (5-fold). At 1 mM g lucose, ATP levels were similar in both cell types, which corresponds to an approximately 2-fold higher concentration in alpha cells (similar to 6.5 m M) than in beta cells (similar to 3 mM), In beta cells, glucose dose-depend ently increased ATP and decreased ADP levels, causing a rise in the ATP/ADP ratio from 2.4 to 11.6 at 1 and 10 mM, respectively. In alpha cells, gluco se did not affect ATP and ADP levels, and the ATP/ADP ratio remained stable around 7.5. In human islets, the ATP/ADP ratio progressively increased bet ween 1 and 10 mM glucose. In duct cells, which often contaminate human isle t preparations, an increase in the ATP/ADP ratio sometimes occurred between 1 and 3 mM glucose. In conclusion, the present observations establish that the regulation of glucagon secretion by glucose does not involve changes i n cu cell adenine nucleotides and further support the role of the ATP/ADP r atio in the control of insulin secretion.