Stress-induced hyperglycemia and hypoinsulinemia are suppressed by sulfonylurea. Predominant role of insulin.

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.