The activity of the β-cell Na+/k+ pump was studied
by using ouabain-sensitive (lmM ouabain) R86b+
influx in β-cell-rich islets of Umeå-ob/ob mice as an
indicator of the pump function. The present results
show that the stimulatory effect of glucose on
ouabain-sensitive R86b+ influx reached its approximate
maximum at 5mM glucose. Pre-treatment of
the islets with 20mM glucose for 60 min strongly
reduced the glucose-induced stimulation of the Na+/k+ pump. Pre-treatment (60 or 180 min) of islets at
0mM glucose, on the other hand, did not affect the
magnitude of the glucose-induced stimulation of R86b+ influx dunng the subsequent 5-min incubation.
Glibenclamide stimulated the ouabain-sensitive
R86b+ uptake in the same manner as glucose.
The stimulatory effect, showed its apparent maximum
at 0.5μM. Pre-treatment (60 min) of islets with
1μM glibenclamide did not reduce the subsequent
stimulation of the ouabain-sensitive R86b+ influx.
The stimulatory effect of glibenclamide and D-glucose
were not .additive, suggesting that they
may have the same mechanism of action. No direct
effect of glibenclamide (0.01-1μM) was observed
on the Na+/k+ ATPase activity in homogenates of
islets. Diazoxide (0.4mM) inhibited the Na+/k+
pump. This effect was sustained even after 60 min of
pre-treatment of islets with 0.4mM diazoxide. The
stimulatory effect of glibenclamide and D-glucose
were abolished by diazoxide. It is concluded
that nutrient as well as non-nutrient insulin secretagogues activate the Na+/k+ pump, probably
as part of the membrane repolarisation process.