title: Grape seed extract supplementation prevents high-fructose diet-induced insulin resistance in rats by improving insulin and adiponectin signalling pathways.
abstract: Recent evidence strongly supports the contention that grape seed extract (GSE) improves hyperglycaemia and hyperinsulinaemia in high-fructose-fed rats. To explore the underlying molecular mechanisms of action, we examined the effects of GSE on the expression of muscle proteins related to the insulin signalling pathway and of mRNA for genes involved in the adiponectin signalling pathway. Compared with rats fed on a normal diet, high-fructose-fed rats developed pathological changes, including insulin resistance, hyperinsulinaemia, hypertriacylglycerolaemia, a low level of plasma adiponectin and a high level of plasma fructosamine. These disorders were effectively attenuated in high-fructose-fed rats supplemented with GSE. A high-fructose diet causes insulin resistance by significantly reducing the protein expression of insulin receptor, insulin receptor substrate-1, Akt and GLUT4, and the mRNA expression of adiponectin, adiponectin receptor R1 (AdipoR1) and AMP-activated protein kinase (AMPK)-α in the skeletal muscle. Supplementation of GSE enhanced the expression of insulin signalling pathway-related proteins, including Akt and GLUT4. GSE also increased the mRNA expression of adiponectin, AdipoR1 and AMPK-α. In addition, GSE increased the mRNA levels of glycogen synthase and suppressed the mRNA expression of glycogen synthase kinase-3-α, causing an increase in glycogen accumulation in the skeletal muscle. These results suggest that GSE ameliorates the defective insulin and adiponectin signalling pathways in the skeletal muscle, resulting in improved insulin resistance in fructose-fed rats.
authors: Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
authors: Aramsri
authors: A
authors: Meeprom
authors: Weerachat
authors: W
authors: Sompong
authors: Wannaporn
authors: W
authors: Suwannaphet
authors: Sirintorn
authors: S
authors: Yibchok-anun
authors: Sirichai
authors: S
authors: Adisakwattana
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics; D052242:Adiponectin / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000009:adverse effects*; D019587:Dietary Supplements; D005632:Fructose / Q000008:administration & dosage* / Q000009:adverse effects*; D051275:Glucose Transporter Type 4 / Q000235:genetics; D006003:Glycogen / Q000096:biosynthesis; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics; D056604:Grape Seed Extract / Q000008:administration & dosage*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054419:Receptors, Adiponectin / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D052242:Adiponectin; D017931:DNA Primers; D004040:Dietary Carbohydrates; D051275:Glucose Transporter Type 4; D056604:Grape Seed Extract; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; C495694:Slc2a4 protein, rat; C504339:adiponectin receptor 1, rat; D005632:Fructose; D006003:Glycogen; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha; D055372:AMP-Activated Protein Kinases