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: To study the effects of a salicylate derivative (triflusal) on insulin sensitivity and insulin secretion.

Design, Setting and Participants: This was a double-blind, randomised, cross-over 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 intravenous glucose tolerance test that was performed after each treatment period. 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 [Ca²⁺]_i level. This was followed by a significantly increase in insulin secretion. In human islets, 200 µM of HTB 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 -cell.