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.
Khan
A
A
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Hong-Lie
C
C
Landau
B R
BR
D000818:Animals; D002463:Cell Membrane Permeability; D003907:Dexamethasone / Q000494:pharmacology*; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D051379:Mice; D008820:Mice, Obese; D008861:Microsomes / Q000201:enzymology*; D009765:Obesity / Q000201:enzymology*; D013045:Species Specificity; D013851:Thinness
D003907:Dexamethasone; D005952:Glucose-6-Phosphatase