AJP - Endocrinology and Metabolism, Vol 250, Issue 3 236-E242, Copyright © 1986 by American Physiological Society
Effect of opiate-receptor blockade on normoglycemic and hypoglycemic glucoregulation
K. M. el-Tayeb, P. L. Brubaker, H. L. Lickley, E. Cook and M. Vranic
By use of the opiate antagonist naloxone, we have examined the hormonal and
metabolic responses to opiate-receptor blockade under basal conditions and
during insulin-induced hypoglycemia in normal dogs. Naloxone treatment had
no measurable effect on glucose concentration, turnover, and norepinephrine
levels, but stimulated plasma epinephrine, glucagon, and cortisol and
inhibited insulin release. Insulin (7 mU X kg-1 X min-1) decreased plasma
glucose to 42 +/- 4 mg/dl due to an initial decrease in glucose production
and an increase in glucose disappearance. Glucose production then
increased, and plasma glucose plateaued. After 50 min of insulin infusion,
epinephrine levels increased 26-fold (P less than 0.05), norepinephrine and
glucagon 3-fold (P less than 0.02), and cortisol 4-fold (P less than 0.01).
Similarly, plasma beta-endorphin and adrenocorticotropin (ACTH) were
elevated (6-fold, P less than 0.01, and 16-fold, P less than 0.05,
respectively). When naloxone was given during insulin-induced hypoglycemia,
there was earlier release of epinephrine, glucagon, beta-endorphin, ACTH,
and cortisol as well as a greater release of glucagon (P less than 0.001)
and cortisol (P less than 0.0001). This resulted in a greater increase in
glucose production (P less than 0.01), thus lessening the insulin-induced
hypoglycemic excursion. In conclusion, in the dog, endogenous opiates may
play a small role in the regulation of basal insulin and glucagon release
and can inhibit the pituitary-adrenal axis under basal conditions and
during hypoglycemia. Thus increased glucose production in response to
insulin-induced hypoglycemia is consistent with the excessive response of
counterregulatory hormones during opiate-receptor blockade.
