Opiate modulation of glucose turnover in dogs

We examined the effect of opiate infusion and of opiate blockage 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-met2 pro5 enkephalinamide (DMPE), a potent morphine-like opiate, 0.5 mus g/kg/min; naloxone, an opiate antagonist, 1.25 mg followed by 10 mus g/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 less than 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 less than 0.05); a transient rise in glucose production (Ra; from 3.2 +/- 0.4 to 4.3 +/- 0.4 mg/kg/min; P less than 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.