Salicylates increase insulin secretion in healthy obese subjects.
BACKGROUND
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.


METHODS
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.


METHODS
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 mum 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 mum 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 beta-cell.
Fernández-Real
José-Manuel
JM
Section of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomédica de Girona, Avinguda de França s/n, Girona, Spain. uden.jmfernandezreal@htrueta.scs.es
López-Bermejo
Abel
A
Ropero
Ana-Belén
AB
Piquer
Sandra
S
Nadal
Angel
A
Bassols
Judit
J
Casamitjana
Roser
R
Gomis
Ramón
R
Arnaiz
Eva
E
Pérez
Iñaki
I
Ricart
Wifredo
W
D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D012459:Salicylates / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D007328:Insulin; D012459:Salicylates; C016167:triflusal; C033502:4-trifluoromethylsalicylic acid; D002097:C-Reactive Protein; D002118:Calcium