Opiate modulation of glucose turnover in dogs

Abstract

We examined the effect of opiate infusion and of opiate blockade on glucose turnover in the basal state, using isotope dilution techniques in trained conscious dogs (n = 5). After a primed-continuous infusion of 3- 3H glucose to steady state specific activity (90 minutes), infusion of one of the following was given: D-met 2 pro 5 enkephalinamide (DMPE), a potent morphine-like opiate, 0.5 μg/kg/min; naloxone, an opiate antagonist, 1.25 mg followed by 10 μg/min; or saline control. Infusion of DMPE led to a fall in glucose from 92 ± 3 to 87 ± 3 mg/dL by 60 minutes ( P < 0.05), associated with a rise in glucose utilization (Rd) from 3.0 ± 0.4 to 3.9 ± 0.6 mg/kg/min by 30 minutes ( P < 0.005); a transient rise in glucose production (Ra; from 3.2 ± 0.4 to 4.3 ± 0.4 mg/kg/min) occurred at 5 minutes ( P < 0.05). Infusion of naloxone did not result in a change of plasma glucose, but caused transient falls at 5 minutes in both Ra (3.5 ± 0.7 to 1.3 ± 0.3 mg/kg/min) and Rd (3.6 ± 0.7 to 1.6 ± 0.4 mg/kg/min; P < 0.05). Changes in counterregulatory hormones did not account for these findings: insulin was unchanged during all infusions; glucagon showed small late rises at 75 minutes during both DMPE and naloxone infusion; cortisol rose by 30 and 15 minutes, respectively, of DMPE and naloxone infusion; epinephrine rose transiently after 5 minutes of naloxone but was unchanged during DMPE, and norepinephrine was unchanged throughout. Saline infusion had no effects on any of these indices. We conclude that a potent opiate with morphine-like effects (DMPE) can lower glucose in dogs by enhancing peripheral glucose utilization independently of hormonal changes.