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Salicylates Increase Insulin Secretion in Healthy Obese Subjects

Department of Diabetes, Endocrinology, and Nutrition (J.-M.F.-R., A.L.-B., J.B., W.R.), Institut d’Investigació Biomédica de Girona, and CIBEROBN Fisiopatología de la Obesidad y Nutrición (J.-M.F.-R., A.L.-B., J.B., W.R.),17007 Girona, Spain; Bioengineering Institute (A.-B.R., A.N.), University of Elche "Miguel Hernández," Elche, 03202 Alicante, Spain; Department of Endocrinology and Hormonal Laboratory (S.P., R.C., R.G.,A.-B.R., A.N.), CIBERDEM Diabetes y Enfermedades Metabólicas, Hospital Clínic, 08036 Barcelona, Spain; and Research and Development Clinical Unit (E.A., I.P.), J. Uriach and Company, 08184 Barcelona, Spain

Address all correspondence and requests for reprints to: J. M. Fernández-Real, M.D., Ph.D., Section of Diabetes, Endocrinology, and Nutrition, Institut d’Investigació Biomédica de Girona, Avinguda de França s/n, 17007 Girona, Spain. E-mail: uden.jmfernandezreal{at}htrueta.scs.es.

Context: Conflicting results on the effects of salicylates on glucose tolerance in subjects with normal glucose tolerance or type 2 diabetes have been reported.

Objective: The objective of the study was to investigate the effects of a salicylate derivative (triflusal) on insulin sensitivity and insulin secretion.

Design, Setting, and Participants: This was a double-blind, randomized, crossover study with three treatment periods corresponding to two dose levels of triflusal and placebo in healthy obese subjects.

Main Outcome Measures: Insulin sensitivity and insulin secretion, evaluated through frequently sampled iv glucose tolerance test that was performed after each treatment period, were measured. Insulin secretion was also evaluated in vitro in mice and human islets of Langerhans.

Results: The administration of triflusal led to decreased fasting serum glucose concentration in the study subjects. Insulin sensitivity did not significantly change after each treatment period. Insulin secretion, however, significantly increased in a dose-dependent fashion after each triflusal treatment period. The administration of 800 µM of the main triflusal metabolite to whole mice islets of Langerhans led to a sustained increase in intracellular calcium concentration level. This was followed by a significantly increase in insulin secretion. In human islets, 200 µM of 2-hydroxy-4-trifluoromethylbenzoic acid was sufficient to increase insulin release.

Conclusions: The administration of a salicylate compound led to lowering of serum glucose concentration. We suggest that this effect was mediated through increased insulin secretion induced by salicylate directly on the β-cell.

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