Fucosylated Chondroitin Sulfate from Sea Cucumber in Combination with Rosiglitazone Improved Glucose Metabolism in the Liver of the Insulin-Resistant Mice

Abstract

This study investigated the effects of a combination of fucosylated chondroitin sulfate (CHS) and rosiglitazone (RSG) on glucose metabolism in the liver of insulin-resistant C57BL/6J mice fed a high-fat high-sucrose diet for 19 weeks. The results showed that the combination (CHS/RSG) synergistically improved body weight gain, liver weight, fasting blood glucose levels, glucose tolerance on an oral glucose tolerance test, serum insulin levels, homeostasis model assessment indexes, and hepatic glycogen content. In liver tissue, CHS/RSG significantly normalized the activities of hexokinase, pyruvate kinase, and glucose-6-phosphatase. In additionally, it increased the mRNA expression of insulin receptors, insulin receptor substrate 2, phosphatidylinositol 3 kinase (PI3K), protein kinase B (PKB), and glycogen synthase, and inhibited glycogen synthase kinase 3β(GSK-3β) mRNA expression in the liver. This suggests that CHS/RSG treatment improves glucose metabolism by modulating metabolic enzymes and strengthening the PI3K/PKB/GSK-3β signal pathway mediated by insulin at the transcriptional level.