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Experimental & Molecular Medicine ; : e30-2013.
Artículo en Inglés | WPRIM | ID: wpr-124614

RESUMEN

Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-alpha-dependent manner. We investigated whether a PPARalpha agonist, fenofibrate, exhibits an additive or synergistic effect on glucose metabolism, independent of its lipid-lowering effect, when added to metformin. Non-obese diabetic Goto-Kakizaki (GK) rats were divided into four groups and treated for 28 days with metformin, fenofibrate, metformin plus fenofibrate or vehicle. The random blood glucose levels, body weights, food intake and serum lipid profiles were not significantly different among the groups. After 4 weeks, metformin, but not fenofibrate, markedly reduced the blood glucose levels during oral glucose tolerance tests, and this effect was attenuated by adding fenofibrate. Metformin increased the expression of the GLP-1 receptor in pancreatic islets, whereas fenofibrate did not. During the intraperitoneal glucose tolerance tests with the injection of a GLP-1 analog, metformin and/or fenofibrate did not alter the insulin secretory responses. In conclusion, fenofibrate did not confer any beneficial effect on glucose homeostasis but reduced metformin's glucose-lowering activity in GK rats, thus discouraging the addition of fenofibrate to metformin to improve glycemic control.


Asunto(s)
Animales , Masculino , Ratas , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Quimioterapia Combinada , Conducta Alimentaria/efectos de los fármacos , Fenofibrato/farmacología , Péptido 1 Similar al Glucagón/agonistas , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Homeostasis/efectos de los fármacos , Inmunohistoquímica , Inyecciones Intraperitoneales , Células Secretoras de Insulina/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Metformina/farmacología , Péptidos/administración & dosificación , Receptores de Glucagón/metabolismo , Ponzoñas/administración & dosificación
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