AJP - Endocrinology and Metabolism, Vol 260, Issue 6 E852-E858, Copyright © 1991 by American Physiological Society
Opiate blockade enhances hypoglycemic counterregulation in normal and insulin-dependent diabetic subjects
S. Caprio, G. Gerety, W. V. Tamborlane, T. Jones, M. Diamond, R. Jacob and R. S. Sherwin
Department of Internal Medicine, Yale University, School of Medicine, New Haven, Connecticut 06510.
To examine the impact of opiate blockade on glucose counterregulation we
performed two hypoglycemic insulin clamp studies with and without naloxone
in healthy subjects and well-controlled insulin-dependent (IDDM) patients
with defective glucose counterregulation. During both studies plasma
glucose fell to 55-60 mg/dl and was then maintained at that level using a
variable glucose infusion. In normal subjects, naloxone increased glucose
production, thereby reducing the exogenous glucose dose needed to maintain
the hypoglycemic plateau. Epinephrine and cortisol responses to
hypoglycemia were increased during naloxone plus insulin compared with
insulin alone; glucagon responses were unaffected. IDDM patients with
suppressed hepatic and hormonal responses to insulin-induced hypoglycemia
also demonstrated greater stimulation of glucose production as well as
epinephrine, growth hormone, and cortisol release during the naloxone
study. In the absence of hypoglycemia, naloxone did not significantly
affect glucose production or glucoregulatory hormones. We conclude that
opiate blockade augments glucoregulatory responses to insulin-induced
hypoglycemia, even in IDDM patients with preexisting defects in glucose
counterregulation. This effect is at least in part due to enhanced
counterregulatory hormone release during hypoglycemia. Endogenous opiates
may modulate hormonal responses during hypoglycemia; their blockade could
provide a means of ameliorating defective counterregulation in IDDM
patients.
