Glucose-6-phosphatase activity in islets from ob/ob and lean mice and the effect of dexamethasone.

In previous studies we demonstrated a much greater rate of glucose cycling (glucose-->glucose-6-P-->glucose) in islets from ob/ob mice than from lean litter mates. Cycling was further augmented by dexamethasone treatment. To determine whether these findings could be accounted for by increased islet glucose-6-phosphatase activity, we have now measured that enzyme's activity in permeabilized and sonicated islets and in islet microsomes. Activity in permeabilized islets from ob/ob mice was 19 times more than from lean litter mates (17.7 +/- 2.9 vs. 0.9 +/- 0.2 pmol/islet/min). Activity was 6 times higher when calculated per microgram of protein or microgram of DNA. Treatment of ob/ob mice with dexamethasone (25 micrograms/daily for 3 days) increased activity 2- to 3-fold. Activities were about twice as much in sonicated as permeabilized islets. There was no difference between glucose-6-phosphatase activity in microsomes prepared from islets of ob/ob and from lean mice, and the activity was relatively low. Thus, permeabilized islets can be used to determine glucose-6-phosphatase activity and study its regulation. The higher glucose cycling in islets of ob/ob mice and its stimulation by dexamethasone can be attributed to increased glucose-6-phosphatase activity.