ISSN:
1432-0428
Keywords:
Opiates
;
naloxone
;
insulin action
;
glucose production
;
glucose utilization
;
counter-regulatory hormones
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary To investigate the influence of opiates on insulin action in vivo, we induced mild physiological hyperinsulinaemia (15–20 mU/l) in five trained conscious dogs in the absence or presence of ongoing infusion with the opiate agonist D-met2-pro5-enkephalinamide (DMPE, 0.5 μg·kg-1· min-1), or the opiate antagonist naloxone (1.25 mg followed by 1 μg· kg-1·min-1). The effects on glucose production and glucose utilization were measured by isotope dilution using 3-3H-glucose. Glucose fell similarly over 30 min in response to insulin in controls (0.021±0.003 mmol·1-1· min-1), and both the DMPE and naloxone studies (0.016±0.002 mmol · 1-1 · min-1 and 0.017±0.003 mmol·1-1 ·min-1, respectively). In control dogs, insulin lowered glucose by transiently suppressing production by 0.028 ±0.006 mmol·kg-1·min-1 at 20–30 min without changing utilization. In contrast, in both the DMPE and naloxone studies insulin lowered glucose by markedly raising utilization at 20 min by 0.094 ±0.017 and 0.139±0.022 mmol·kg-1·min-1, respectively. Furthermore, insulin failed to suppress production in both DMPE and naloxone studies and, as plasma glucose fell, production rose in both treatment groups at 20 min by 0.045 ±0.012 and 0.089 ±0.022 mmol · kg-1 · min-1 respectively. The counter-regulatory hormone glucagon was transiently suppressed by insulin at 20 min in controls, but not in the treatment groups; cortisol and adrenaline rose at 30 and 45 min respectively in the naloxone group only. No other changes were noted in counterregulatory hormones. Thus hormonal changes do not appear to account for the early pronounced rise in glucose utilization leading to the fall in glucose in the DMPE and naloxone studies. We conclude that the morphine-like agent DMPE and high doses of the opiate antagonist naloxone modulate insulin-induced glucose fluxes in vivo, promoting both glucose utilization and production. These effects may be direct or indirect, and may serve a function in the redistribution of glucose during stress responses.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00252266
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