RESUMO
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.
Assuntos
Sinalização do Cálcio/fisiologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Curcumina/química , Curcumina/farmacologia , Células Enteroendócrinas/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Linhagem Celular , Células Enteroendócrinas/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Relação Estrutura-AtividadeRESUMO
Blueberries or bilberries contain large amounts of anthocyanins, making them one of the richest sources of dietary anthocyanin. These berries are widely consumed as fresh and dried fruits, jams, or juices. Considerable attention has been focused on the health benefits of bilberry fruits beyond their antioxidant content or their ability to improve vision. In this study, we tested the effect of dietary bilberry extract (BBE) on hyperglycemia and insulin sensitivity in type 2 diabetic mice. We found that dietary BBE ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase (AMPK). Dietary BBE significantly reduced the blood glucose concentration and enhanced insulin sensitivity. AMPK was activated in white adipose tissue (WAT), skeletal muscle, and the liver of diabetic mice fed BBE. This activation was accompanied by upregulation of glucose transporter 4 in WAT and skeletal muscle and suppression of glucose production and lipid content in the liver. At the same time, acetyl-CoA carboxylase was inactivated and PPARalpha, acyl-CoA oxidase, and carnitine palmitoyltransferase-1A were upregulated in the liver. These changes resulted in improved hyperglycemia and insulin sensitivity in type 2 diabetes. These findings provide a biochemical basis for the use of bilberry fruits and have important implications for the prevention and treatment of type 2 diabetes via activation of AMPK.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antocianinas/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Vaccinium myrtillus/química , Adiponectina/genética , Adiponectina/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Antocianinas/farmacologia , Glicemia , Peso Corporal , Dieta , Ingestão de Alimentos , Metabolismo Energético , Regulação Enzimológica da Expressão Gênica , Gluconeogênese , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Fígado/metabolismo , Masculino , Camundongos , Músculo Esquelético/metabolismo , Extratos Vegetais/química , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/genética , Proteínas Plasmáticas de Ligação ao Retinol/metabolismoRESUMO
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.