RESUMEN
Glucagon-like peptide-1 (GLP-1) is a hormone secreted from enteroendocrine L-cells. Enhancing GLP-1 action is an important target for prevention and treatment of type 2 diabetes. Several approaches (GLP-1 analogs, dipeptidyl peptidase IV inhibitors) are being used to develop therapeutic agents using GLP-1 action for the treatment of diabetes. However, an alternative approach is to increase endogenous GLP-1 secretion through modulation of the secretory mechanism in intestinal L cells by pharmaceutical agents or dietary ingredients. In the present study, we demonstrate that curcumin, a yellow pigment isolated from the rhizomes of Curcuma longa L, significantly increases GLP-1 secretion in GLUTag cells, and we clarified the structure-activity relationship using curcumin derivatives. Also, concerning the secretory mechanism, the significant increase in GLP-1 secretion by curcumin involved the Ca(2+)-Ca(2+)/calmodulin-dependent kinase II pathway, and was independent of extracellular signal-regulated kinase, PKC, and the cAMP/PKA-related pathway. These findings provide a molecular mechanism for GLP-1 secretion mediated by foods or drugs, and demonstrate a novel biological function of curcumin in regards to GLP-1 secretion.
Asunto(s)
Señalización del Calcio/fisiología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Curcumina/química , Curcumina/farmacología , Células Enteroendocrinas/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Señalización del Calcio/efectos de los fármacos , Línea Celular , Células Enteroendocrinas/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Relación Estructura-ActividadRESUMEN
Black soybean seed coat has abundant levels of polyphenols such as anthocyanins (cyanidin 3-glucoside; C3G) and procyanidins (PCs). This study found that dietary black soybean seed coat extract (BE) ameliorates hyperglycemia and insulin sensitivity via the activation of AMP-activated protein kinase (AMPK) in type 2 diabetic mice. Dietary BE significantly reduced blood glucose levels and enhanced insulin sensitivity. AMPK was activated in the skeletal muscle and liver of diabetic mice fed BE. This activation was accompanied by the up-regulation of glucose transporter 4 in skeletal muscle and the down-regulation of gluconeogenesis in the liver. These changes resulted in improved hyperglycemia and insulin sensitivity in type 2 diabetic mice. In vitro studies using L6 myotubes showed that C3G and PCs significantly induced AMPK activation and enhanced glucose uptake into the cells.