title: Fucosylated chondroitin sulfate from sea cucumber improves glucose metabolism and activates insulin signaling in the liver of insulin-resistant mice.
abstract: This study investigated the effects of fucosylated chondroitin sulfate (CHS) isolated from sea cucumber on glucose metabolism and insulin signaling in the liver of insulin-resistant C57BL/6 mice fed a high-fat, high-sucrose diet (HFSD). Male C57BL/6J mice were randomly assigned into six groups: control; HFSD; 1 mg RSG/kg·body weight (RSG); 80 mg CHS/kg · body weight (CHS); 20 mg CHS+1 mg RSG/kg · body weight (20 CHS+RSG); and 80 mg CHS+1 mg RSG/kg · body weight (80 CHS+RSG). Blood glucose, insulin parameters, glucose metabolism-related enzymes activities and insulin-signaling transducers in the liver were analyzed at 19 weeks. Results showed that CHS significantly decreased body weight gain, adipose tissue weight, and fasting blood glucose and serum insulin levels in insulin-resistant mice. Rosiglitazone (RSG) is an effective thiazolidinedione hypoglycemic agent, and CHS synergistically enhanced the effect of RSG. CHS feeding normalized the activities of hexokinase, pyruvate kinase, glycogen phosphorylase, glucose-6-phosphatase, and increased glycogen reserves in the liver. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that CHS promoted the mRNA expression of insulin receptors (IR), insulin receptor substrate 2 (IRS-2), phosphatidylinositol 3 kinase (PI3K), protein kinase B (PKB), and glycogen synthase (GS) in the liver of insulin resistant mice, and inhibited glycogen synthase kinase-3 (GSK-3β) mRNA expression. The results suggested that CHS treatment improved glucose metabolism by modulating metabolic enzymes and promoting the PI3K/PKB/GSK-3β signaling pathway mediated by insulin at the transcriptional level. These results provided strong justification for the development of CHS as a functional food.
authors.affiliation: 1 College of Food Science and Engineering, Ocean University of China , Qingdao, China .
authors.forename: Shi-Wei
authors.initials: SW
authors.lastname: Hu
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Tian
authors.forename: Yao-Guang
authors.initials: YG
authors.lastname: Chang
authors.forename: Zhao-Jie
authors.initials: ZJ
authors.lastname: Li
authors.forename: Chang-Hu
authors.initials: CH
authors.lastname: Xue
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Wang
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D059305:Diet, High-Fat / Q000009:adverse effects; D019422:Dietary Sucrose / Q000008:administration & dosage; D004357:Drug Synergism; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000077154:Rosiglitazone; D012616:Sea Cucumbers / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D019422:Dietary Sucrose; D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526298:Irs2 protein, mouse; D045162:Thiazolidinediones; C517150:fucosylated chondroitin sulfate; D000077154:Rosiglitazone; D006003:Glycogen; D002809:Chondroitin Sulfates; D006006:Glycogen Synthase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: blood glucose level; fucosylated chondroitin sulfate; glucose metabolism; glycogen content; insulin signaling; sea cucumber