Sodium salicylate potentiates neurohumoral responses to insulin-induced hypoglycemia

S. Metz, J. Halter, R. P. Robertson

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14 Scopus citations


Prostaglandin E (PGE) has been shown to modulate the release of norepinephrine (NOREPI), epinephrine (EPI), and glucagon (IRG) in animal studies in vitro, but a physiological modulatory role has not been demonstrated in vivo in humans. Since our previous studies suggested that PGE selectively alters insulin responses to glycemic stimuli, we examined the NOREPI, EPI, and IRG responses of six normal male subjects to a glucose signal (insulin-induced hypoglycemia) before and during infusions of sodium salicylate (SS), an inhibitor of PGE synthesis. Peak EPI levels (control, 338 ± 122; SS, 687 ± 115 pg/ml; mean ± SEM, P <0.01) and EPI areas from 0-120 min (control, 8.4 ± 3.1; SS, 18.7 ± 3.3 ng/ml.2 h; P <0.02) were more than doubled during SS. NOREPI areas were augmented, but only in the first 45 min (2.74 ± 0.74 vs. 5.35 ± 0.49 ng/ml.45 min; P <0.05). These differences were found despite the fact that the mean of the individual glucose nadirs (34 ± 3 vs. 32 ± 2 mg/dl) and the rate of fall of glucose were not altered by SS. The effects on EPI were not due to altered catabolism, since SS did not significantly alter EPI levels achieved during exogenous infusion of EPI (3 μg/min for 45 min) in five subjects or the calculated half-life of EPI after the discontinuation of EPI infusion. Basal and peak IRG levels during hypoglycemia (control, 125 ± 29; SS, 228 ± 28 pg/ml; P <0.01) and IRG areas were also augmented by SS. The sweating response to hypoglycemia was augmented in both extent and magnitude by SS. We conclude that SS augments the neural (adrenergic and cholinergic) and humoral responses to hypoglycemia. The drug appears to improve the recognition of and/or augment the response to a given degree of hypoglycemia, an effect which could be due to the inhibition of PGE synthesis.

Original languageEnglish (US)
Pages (from-to)93-100
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number1
StatePublished - 1980


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