Based on the in vitro blockade of adrenal
catecholamines release by sulfonylurea, we searched for an anti-stress activity of this
drug. Stress-induced
hyperglycemia and
insulin inhibition were employed as
adrenergic stress indicators. A standard dose of the oral sulfonylurea
glipizide (200 micrograms/100 g), administered 15 min before a 1-h restraint stress to intact or 80% pancreatectomized rats, produced total suppression of the stress-induced
hyperglycemia-hypoinsulinemia, an effect followed by a significant post-stress
hypoglycemia of 1 h duration. The latter effect was elicited by all the sulfonylureas assayed. In the 80% pancreatectomized rats,
glipizide nearly halved the increases in plasma
catecholamines at 30 min of stress, but did not modify those attained at 60 min, when glycemia was decreasing and insulinemia was still increasing. Moreover, behavioral experiments in intact stressed rats showed that the
adrenergic overt behavior inhibition caused by
propranolol was not produced either by
glipizide or
insulin, reinforcing that
glipizide affect was not mediated by
catecholamine inhibition. These findings suggest a blockade of
catecholamines hepatic receptors by the anticipated
insulin release induced by sulfonylurea. Thus,
insulin fully dominated when
insulin and
catecholamines were administered in a stress-like sequence. A confirmation of these findings in diabetic patients subjected to surgical stress would allow a new therapeutic application of sulfonylurea. It is concluded that an anticipated
insulin release plus an
insulin dominant role over
catecholamines activity might explain the anti-stress effect of sulfonylurea.