The effects of oral hypoglycaemic drugs,
SPC-703 (n-/p-toluenesulphonyl/-5-methyl-2-pirazoline-1-carbonami de) and
tolbutamide on
insulin binding and
glucose metabolism by isolated adipocytes were studied. After 10 days of administration of both sulphonylurea derivatives, no differences were observed in
insulin concentration between both experimental and the control groups of animals, despite a significant fall in
blood glucose level.
SPC-703 and
tolbutamide in concentrations of 1 mM added in vitro to the
suspension of adipocytes had no effect on
insulin binding or on basal and
insulin simulated
glucose metabolism. Daily administration of 300 mg/kg
body weight of
SPC-703 or
tolbutamide for 10 days resulted in 48% and 34% increase of specific binding of
insulin by adipocytes, respectively. From the Scatchard plot analysis we noted that the increase of binding resulted from increased affinity of
insulin receptors for
hormone. Simultaneous increase in basal and
insulin stimulated
glucose metabolism by adipocytes, as measured by 14CO2 production and 14C incorporation into cellular
lipids, was observed. The results indicate that hypoglycaemic action of sulphonylureas may be explained by increased affinity of
insulin receptors and the stimulating action of these compounds on peripheral
glucose metabolism.