chondroitin-sulfates and Insulin-Resistance

Several studies have isolated chondroitin sulphate (CHS) from sharks' jaws or cartilage. However, there has been little research on CHS from shark skin. In the present study, we extracted a novel CHS from

Topics: Animals; Blood Glucose; Chondroitin Sulfates; Insulin Resistance; Sharks; Spectroscopy, Fourier Transform Infrared

Hydrogen sulfide (H

Topics: Animals; Chondroitin Sulfates; Desulfovibrio; Diet, High-Fat; Hydrogen Sulfide; Insulin Resistance; Liver; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Proto-Oncogene Proteins c-akt

A fucosylated chondroitin sulfate was isolated from the body wall of sea cucumber Stichopus japonicus (FCSsj), whose structure was characterized by NMR spectroscopy and HILIC-FTMS. At the ratio of 1.00:0.26:0.65, three fucosyl residues were found: 2,4-disulfated-fucose (Fuc2,4S), 4-sulfated-fucose (Fuc4S) and 3,4-disulfated-fucose (Fuc3,4S), which were only linked to the O-3 of glucuronic acid residues (GlcA). Besides mono-fucosyl moieties, di-fucosyl branches, namely Fuc2,4Sα(1→3)Fuc4S, were also found to be attached to the O-3 of GlcA. The antidiabetic activity of FCSsj was evaluated using glucosamine induced insulin resistant (IR) Hep G2 cells in vitro. It was found that FCSsj significantly promoted the glucose uptake and glucose consumption of IR-Hep G2 cells in a dose-dependent manner, and could alleviate the cell damage. Furthermore, FCSsj could promote the glycogen synthesis in the glucosamine-induced IR-Hep G2 cells. These results provided a supplement for studying the antidiabetic activity of FCSsj.

Topics: Animals; Chondroitin Sulfates; Fucose; Glucose; Glucuronic Acid; Glycogen; Hep G2 Cells; Humans; Hypoglycemic Agents; Insulin Resistance; Magnetic Resonance Spectroscopy; Sea Cucumbers; Stichopus

Endoplasmic reticulum (ER) stress-associated inflammation positively contributes to insulin resistance. It is also known that fucosylated chondroitin sulphate from Cusumaria frondosa (Cf-CHS) can mitigate insulin resistance; however, its effects on ER stress and inflammation are not well understood. Therefore, we investigated whether Cf-CHS-influenced ER stress, inflammatory response and signaling in insulin-resistant mice. Our results showed that Cf-CHS lowered serum and hepatic ROS, NO, and FFA levels. Furthermore, Cf-CHS decreased serum proinflammatory cytokines TNF-α, CRP, MIP-1, IL-1β and IL-6 concentrations as well as their hepatic mRNA expression, and increased the anti-inflammatory cytokine IL-10 levels. Moreover, Cf-CHS reduced the ER stress markers Bip, ATF6, PERK, and XBP1 mRNA or protein expression, and PERK, eIF2α, and IRE1α phosphorylation. These reductions were accompanied by a reduced activation of JNK1 and IKKβ, NFκB nuclear translocation, and IR/IRS-2 serine phosphorylation in Cf-CHS-treated mice. These findings suggested that the Cf-CHS supplementary-induced alleviation of RE stress-associated inflammation could be the mechanism responsible for its beneficial effects against insulin resistance.

Topics: Animals; Chondroitin Sulfates; Diabetes Mellitus, Type 2; Endoplasmic Reticulum Stress; I-kappa B Kinase; Insulin Resistance; Interleukin-10; Interleukin-1beta; Interleukin-6; Liver; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Sea Cucumbers

This study was to investigate the effects of fucosylated chondroitin sulfate (CHS) from sea cucumber on insulin sensitivity in skeletal muscle of type 2 diabetic mice induced by a high-fat high-sucrose diet (HFSD). CHS supplementation for 19 wk significantly improved insulin sensitivity by 20%, and reduced blood glucose and insulin levels. Western blotting assay showed that CHS significantly increased insulin-stimulated glucose transporter 4 (GLUT4) translocation to 1.7-fold, phosphorylation of phosphoinositide 3-kinase (PI3K) at p85 to 5.0-fold, protein kinase B (PKB) at Ser473 to 1.5-fold, and Thr308 to 1.6-fold in skeletal muscle. However, PI3K, PKB, and GLUT4 total proteins expression were unchangeable. In addition, qRT-PCR analysis proved that the insulin signaling was activated by CHS treatment, showing the increased mRNA expressions of glucose uptake-related key genes. It indicated that CHS improved insulin sensitivity by activation of PI3K/PKB signaling in skeletal muscle of type 2 diabetic mice. Identification of potential mechanism by which CHS increased insulin sensitivity might provide a new functional food or pharmaceutical application of sea cucumber.

Topics: Animals; Blood Glucose; Chondroitin Sulfates; Diabetes Mellitus, Experimental; Glucose Transporter Type 4; Hyperinsulinism; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Sea Cucumbers; Signal Transduction

In this study, we investigated the improvement of fucosylated chondroitin sulfate (CHS) from the cucumber Acaudina molpadioides on hyperglycemia in skeletal muscle of insulin resistant mice. CHS, rosiglitazone (RSG), and their combinations were supplemented to high-fat high-sucrose diet (HFSD)-fed C57BL/6J mice for 19 weeks. The results showed that CHS treatment remarkably decreased blood glucose level and insulin resistance. The glucose metabolism-related genes expressions at the transcriptional level were apparently increased in skeletal muscle. Although the total protein expressions of IR-β, IRS-1, PI3K, PKB and GLUT4 in skeletal muscle were not affected, insulin-stimulated GLUT4 translocation and phosphorylation of Tyr-IR-β, Tyr612-IRS-1, p85-PI3K, Ser473-PKB, and Thr308-PKB were significantly increased by CHS supplement. Additionally, combination of CHS and RSG produced synergistic effects on anti-hyperglycemia. These results indicate that CHS can alleviate hyperglycemia via activation of the PKB/GLUT4 signaling pathway in skeletal muscle of insulin resistant mice.

Topics: Animals; Biological Factors; Blood Glucose; Chondroitin Sulfates; Glucose Transporter Type 4; Humans; Hyperglycemia; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase Kinases; Muscle, Skeletal; Sea Cucumbers; Signal Transduction

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.

Topics: Animals; Blood Glucose; Body Weight; Chondroitin Sulfates; Diet, High-Fat; Drug Synergism; Drug Therapy, Combination; Gene Expression Regulation; Glucose Tolerance Test; Glucose-6-Phosphatase; Glycogen; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hexokinase; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Liver; Male; Mice; Mice, Inbred C57BL; Organ Size; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Pyruvate Kinase; Receptor, Insulin; Rosiglitazone; Sea Cucumbers; Signal Transduction; Thiazolidinediones

Glucosamine (G), often combined with chondroitin sulfate (CS), is a popular natural supplement used widely to treat osteoarthritis. However, use of glucosamine has been linked to development of insulin resistance. To assess the association between glucosamine and insulin resistance more closely, we challenged two rat strains highly sensitive to sugar-induced insulin resistance-Sprague-Dawley (SD) and Spontaneously Hypertensive (SHR) rats. Since elevations of systolic blood pressure (SBP) have been found to be an early and highly sensitive sign of insulin resistance in these two rat strains, we used this parameter as our primary endpoint. Four groups of both rat strains received either no agent (control), G, CS, or a combination of both for 9 weeks. The intake of each agent was calculated to be approximately 3-7 times comparable to human dose. Throughout the study, SBP of both strains consuming the two ingredients alone and in combination were not elevated. Rather, they were significantly lower than control, contrary to what is found in glucose-induced insulin resistance in rats. Over the study period, body weights of the four groups of SD and SHR did not vary significantly. Furthermore, no consistent trends in circulating glucose concentrations were found among the four different groups in the two strains after oral challenge with glucose. Finally, no significant histological differences were found in hearts, kidneys, and livers among the various groups of SHR and SD. From the above result, we conclude that glucosamine and chondroitin sulfate given alone or together do not produce insulin resistance or other related perturbations in two rat strains highly sensitive to sugar-induced insulin resistance.

Topics: Administration, Oral; Animals; Blood Glucose; Blood Pressure; Body Weight; Chondroitin Sulfates; Glucosamine; Glucose; Hypertension; Insulin Resistance; Male; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Time Factors