1. The effect of
BTS 67 582, a novel
antidiabetic agent, has been evaluated on plasma
glucose and plasma
insulin in normal and
streptozotocin-induced diabetic rats. 2.
BTS 67 582 (3 to 300 mg kg-1, p.o.) caused a dose- and time-dependent reduction in plasma
glucose and an increase in plasma
insulin in both fasted and
glucose-loaded normal rats. The ED50 for the
glucose lowering effect of
BTS 67 582 in fasted rats was 37.6, 18.4 and 18.5 mg kg-1 at 1, 2 and 4 h after administration respectively. 3. In
streptozotocin-induced (50 mg kg-1, i.v.) diabetic rats,
BTS 67 582 (37-147 mg kg-1, p.o.) caused significant reductions of plasma
glucose following a
glucose load, whereas
glibenclamide (100 mg kg-1, p.o.) was ineffective.
BTS 67 582 significantly increased plasma
insulin compared to controls whereas
glibenclamide did not. 4.
BTS 67 582 did not displace [3H]-
glibenclamide from its binding sites in rat brain, guinea-pig ventricle or the HIT-T15
insulinoma beta-cell line.
BTS 67 582 does not therefore appear to modulate its action via an effect on the 'sulphonylurea' receptor. 5. In fasted rats, the
glucose lowering effect of
BTS 67 582 (100 mg kg-1 p.o.) and
glibenclamide (1 mg kg-1, p.o.) were antagonized by
diazoxide (30 mg kg-1, i.p.). In addition
BTS 67 582, like
glibenclamide, caused a dose-dependent rightward shift of
cromakalim-induced relaxation of
noradrenaline precontracted rat aortic strips, suggesting the involvement of
KATP channels. 6. In summary,
BTS 67 582 produces a
blood glucose-lowering effect in normal and
streptozotocin-induced diabetic rats associated with increased
insulin concentrations. This effect appears to be due to a blockade of
ATP-sensitive potassium channel activity via a different binding site to that of
glibenclamide.