title: Cocoa-rich diet ameliorates hepatic insulin resistance by modulating insulin signaling and glucose homeostasis in Zucker diabetic fatty rats.
abstract: Insulin resistance is the primary characteristic of type 2 diabetes and results from insulin signaling defects. Cocoa has been shown to exert anti-diabetic effects by lowering glucose levels. However, the molecular mechanisms responsible for this preventive activity and whether cocoa exerts potential beneficial effects on the insulin signaling pathway in the liver remain largely unknown. Thus, in this study, the potential anti-diabetic properties of cocoa on glucose homeostasis and insulin signaling were evaluated in type 2 diabetic Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed a control or cocoa-rich diet (10%), and Zucker lean animals received the control diet. ZDF rats supplemented with cocoa (ZDF-Co) showed a significant decrease in body weight gain, glucose and insulin levels, as well as an improved glucose tolerance and insulin resistance. Cocoa-rich diet further ameliorated the hepatic insulin resistance by abolishing the increased serine-phosphorylated levels of the insulin receptor substrate 1 and preventing the inactivation of the glycogen synthase kinase 3/glycogen synthase pathway in the liver of cocoa-fed ZDF rats. The anti-hyperglycemic effect of cocoa appeared to be at least mediated through the decreased levels of hepatic phosphoenolpyruvate carboxykinase and increased values of glucokinase and glucose transporter 2 in the liver of ZDF-Co rats. Moreover, cocoa-rich diet suppressed c-Jun N-terminal kinase and p38 activation caused by insulin resistance. These findings suggest that cocoa has the potential to alleviate both hyperglycemia and hepatic insulin resistance in type 2 diabetic ZDF rats.
authors: Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition, Consejo Superior de Investigaciones Científicas, José Antonio Novais 10, Ciudad Universitaria, 28040 Madrid, Spain.
authors: Isabel
authors: I
authors: Cordero-Herrera
authors: Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition, Consejo Superior de Investigaciones Científicas, José Antonio Novais 10, Ciudad Universitaria, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, 28029 Madrid, Spain.
authors: María Ángeles
authors: MÁ
authors: Martín
authors: Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, 28029 Madrid, Spain; Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors: Fernando
authors: F
authors: Escrivá
authors: Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, 28029 Madrid, Spain; Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors: Carmen
authors: C
authors: Álvarez
authors: Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition, Consejo Superior de Investigaciones Científicas, José Antonio Novais 10, Ciudad Universitaria, 28040 Madrid, Spain.
authors: Luis
authors: L
authors: Goya
authors: Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition, Consejo Superior de Investigaciones Científicas, José Antonio Novais 10, Ciudad Universitaria, 28040 Madrid, Spain. Electronic address: s.ramos@ictan.csic.es.
authors: Sonia
authors: S
authors: Ramos
mesh_terms: D000818:Animals; D002099:Cacao / Q000737:chemistry*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000178:diet therapy* / Q000378:metabolism; D019587:Dietary Supplements; D006006:Glycogen Synthase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006943:Hyperglycemia / Q000517:prevention & control; D006946:Hyperinsulinism / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D009765:Obesity / Q000150:complications / Q000517:prevention & control; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011897:Random Allocation; D011922:Rats, Mutant Strains; D011924:Rats, Zucker
chemical_list: D007004:Hypoglycemic Agents; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D006006:Glycogen Synthase; D038362:Glycogen Synthase Kinase 3
keywords: Cocoa; Glucose homeostasis; Glucose tolerance; Insulin resistance; Insulin signaling pathway; Type 2 diabetic ZDF rats