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Related Experiment Videos

Morphine-3-glucuronide: hyperglycemic and neuroendocrine potentiating effects

Y Hashiguchi1, P E Molina, N N Abumrad

  • 1Department of Surgery, SUNY at Stony Brook 11794-8191, USA.

Brain Research
|October 2, 1995
PubMed
Summary

Morphine metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) have different effects on glucose metabolism. M3G causes hyperglycemia via a non-hormonal pathway, while M6G and morphine induce hyperglycemia with hormonal changes.

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Area of Science:

  • Neuropharmacology
  • Endocrinology
  • Metabolism

Background:

  • Morphine-6-glucuronide (M6G) is more potent than morphine (MOR), while morphine-3-glucuronide (M3G) is inactive and may antagonize MOR's effects.
  • The central nervous system (CNS) interactions of MOR metabolites on metabolic and hormonal axes are not fully understood.

Purpose of the Study:

  • To investigate the central nervous system (CNS) effects of M3G and M6G on glucose kinetics and hormonal responses.
  • To elucidate the distinct mechanisms underlying hyperglycemia induced by MOR and its glucuronides.

Main Methods:

  • Whole body glucose kinetics were measured in conscious, unrestrained rats with chronic catheters.
  • Intracerebroventricular (i.c.v.) injections of M3G, M6G, or MOR were administered, with or without M3G pretreatment.

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Main Results:

  • i.c.v. M3G caused rapid hyperglycemia, increased glucose appearance and disappearance rates, and stimulated metabolic clearance rate without altering hormone levels.
  • i.c.v. M6G and MOR induced hyperglycemia associated with elevated catecholamine and corticosterone levels.
  • M3G pretreatment enhanced hyperglycemia and hormonal responses (norepinephrine, epinephrine, lactate) to both MOR and M6G.

Conclusions:

  • M3G-induced hyperglycemia appears to operate via a non-opiate, non-hormonal mechanism.
  • M6G and MOR effects on glucose metabolism are linked to catecholamine and corticosterone release, potentiated by M3G.
  • Morphine glucuronidation plays a modulatory role, influencing the metabolic and hormonal interplay between morphine and its metabolites.