The changes in adenine nucleotides measured in glucose-stimulated rodent islets occur in β cells but not in α cells and are also observed in human islets

Abstract

Glucose metabolism by pancreatic β and α cells is essential for stimulation of insulin secretion and inhibition of glucagon secretion. Studies using rodent islets have suggested that the ATP/ADP ratio serves as second messenger in β cells. This study compared the effects of glucose on glucose oxidation ([U- 14C]glucose) and adenine nucleotides (luminometric method) in purified rat α and β cells. The rate of glucose oxidation at 1 mM glucose was higher in β than α cells (4.5-fold, i.e. ~2-fold after normalization for cell size). It was more strongly stimulated by 10 mM glucose in β cells (9-fold) than in α cells (5-fold). At 1 mM glucose, ATP levels were similar in both cell types, which corresponds to an approximately 2-fold higher concentration in α cells (-6.5 mM) than in cells (~3 mM). In β cells, glucose dose-dependently 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 a cells, glucose 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 between 1 and 10 mM glucose. In duct cells, which often contaminate human islet 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 in α cell adenine nucleotides and further support the role of the ATP/ADP ratio in the control of insulin secretion.