Salicylates increase insulin secretion in healthy obese subjects

被引:32
作者
Fernandez-Real, Jose-Manuel [1 ,2 ]
Lopez-Bermejo, Abel [2 ]
Ropero, Ana-Belen [3 ,4 ,5 ]
Piquer, Sandra [4 ,5 ]
Nadal, Angel [3 ,4 ,5 ]
Bassols, Judit [2 ]
Casamitjana, Roser [4 ,5 ]
Gomis, Ramon [4 ,5 ]
Arnaiz, Eva [6 ]
Perez, Inaki [6 ]
Ricart, Wifredo [2 ]
机构
[1] Inst Invest Biomed Girona, Sect Diabet Endocrinol & Nutr, Dept Diabet Endocrinol & Nutr, Girona 17007, Spain
[2] CIBEROBN Fisiopatol Obesidad & Nutr, Girona 17007, Spain
[3] Univ Elche Miguel Hernandez, Bioengn Inst, Alicante 03202, Spain
[4] Hosp Clin Barcelona, Dept Endocrinol, Barcelona 08036, Spain
[5] Hosp Clin Barcelona, Hormonal Lab, CIBERDEM Diabet & Enfermedades Metab, Barcelona 08036, Spain
[6] J Uriach & Co, Res & Dev Clin Unit, Barcelona 08184, Spain
关键词
D O I
10.1210/jc.2007-1212
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mu M 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 mu M 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.
引用
收藏
页码:2523 / 2530
页数:8
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