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.
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