Abstract
Feeding inhibition by the opiate antagonist naloxone is enhanced in diabetes and blunted by hypoglycaemia. The relative roles of glucose and insulin in these phenomena remain unclear. We investigated possible regulation of the opiate receptor by glucose and/or insulin by examining in vitro effects of glucose(5mM or 10mM) or insulin(luM), on tritiated naloxone binding to rat brain membranes. In whole brain membranes, glucose 5mM and 10mM increased 3-H-naloxone binding by 10+/−4%(n=4) and 38+/−9%(n=3). Insulin increased 3-H-naloxone binding by 27+/−3%(n=5). In hypothalamus, rich in opiate receptors, glucose(10mM) and insulin(luM) increased opiate binding by 17+/−3%(n=4) and 29+/−11%(n=3) respectively. Insulin was maximally effective at 0.2nM, enhancing binding by 57%. Glucose and insulin both enhanced the average affinity (Kd) for naloxone binding: control 0.76nM; glucose(10mM) 0.38nM; insulin(luM)0.32nM. Anti-insulin receptor antibody and insulin analogue D-ala,D-asp-insulin both mimicked the insulin effect, while proinsulin was weakly effective; hGH and IGF did not effect opiate binding. Modest in vivo modulation was demonstrated following intra-ventricular infusion of 10mM glucose, luM insulin, or artificial CSF for 6 days: Binding of 3-H-naloxone to hypothalamus was enhanced by 11+/−6% following glucose infusion (n=3) and 14+/−13% following insulin infusion (n=3).
Conclusion: Glucose and insulin enhance naloxone binding to brain receptors. The mechanism involves an affinity increase of opiate receptors; insulin acts via its own receptor. These findings suggest that insulin and glucose in the brain may play a role in Modulating opiate receptors and their actions.
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Werther, G., Hogg, A. 89 GLUCOSE AND INSULIN MODULATE BRAIN OPIATE RECEPTORS. Pediatr Res 19, 618 (1985). https://doi.org/10.1203/00006450-198506000-00109
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DOI: https://doi.org/10.1203/00006450-198506000-00109