Concentration Dependence and Time Course of the Effects of Glucose on Adenine and Guanine Nucleotides in Mouse Pancreatic Islets

Abstract

Changes in the ATP:ADP ratio in pancreatic B cells may participate in the regulation of insulin secretion by glucose. Here, we have investigated the possible role of guanine nucleotides. Mouse islets were incubated in a control medium (when K+-ATP channels are the major site of regulation) or in a high K+ medium (when glucose modulates the effectiveness of cytosolic Ca2+ on exocytosis). Glucose induced a concentration-dependent (0-20 m) increase in GTP and a decrease in GDP in both types of medium, thus causing a progressive rise of the GTP:GDP ratio. ATP and ADP levels were 4-5-fold higher but varied in a similar way as those of guanine nucleotides. Insulin secretion was inversely correlated with ADP and GDP levels and positively correlated with the ATP:ADP and GTP:GDP ratios between 6 and 20 m glucose in control medium and between 0 and 20 m glucose in high K+ medium. The increases in the GTP:GDP and ATP:ADP ratios induced by a rise of glucose were faster than the decreases induced by a fall in glucose, but the changes of both ratios were again parallel. In conclusion, glucose causes large, concentration-dependent changes in guanine as well as in adenine nucleotides in islet cells. This raises the possibility that both participate in the regulation of nutrient-induced insulin secretion.