norathyriol has been researched along with Insulin-Resistance* in 2 studies
2 other study(ies) available for norathyriol and Insulin-Resistance
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Mangiferin and its aglycone, norathyriol, improve glucose metabolism by activation of AMP-activated protein kinase.
Mangiferin has been reported to possess antidiabetic activities. Norathyriol, a xanthone aglycone, has the same structure as mangiferin, except for a C-glucosyl bond. To our best knowledge, no study has been conducted to determine and compare those two compounds on glucose consumption in vitro.. In this study, the effects of norathyriol and mangiferin on glucose consumption in normal and insulin resistance (IR) L6 myotubes were evaluated. Simultaneously, the potential mechanism of this effect was also investigated.. Normal or IR L6 myotubes were incubated with norathyriol (2.5 ∼ 10 μM, 0.625 ∼ 2.5 μM), mangiferin (10 ∼ 40 μM, 2.5 ∼ 10 μM) or rosiglitazone (20 μM) and/or 0.05 nM insulin for 24 h, respectively. The glucose consumption was assessed using the glucose oxidase method. Immunoblotting was performed to detect protein kinase B (PKB/Akt) and AMP-activated protein kinase (AMPK) phosphorylation in L6 myotubes cells.. Norathyriol and mangiferin treatment alone increased the glucose consumption 61.9 and 56.3%, respectively, in L6 myotubes and made additional increasing with 0.05 nM insulin. In IR L6 myotubes, norathyriol treatment made increasing with or without insulin, mangiferin treatment also made increasing but only when co-treated with insulin. Immunoblotting results showed that norathyriol and mangiferin produced an increase of 1.9 - and 1.8-fold in the phosphorylation levels of the AMPK, but not in Akt.. Our findings suggest that norathyriol and mangiferin could improve the glucose utilization and insulin sensitivity by up-regulation of the phosphorylation of AMPK. Norathyriol may be considered as an active metabolite responsible for the antidiabetic activity of mangiferin. Topics: AMP-Activated Protein Kinases; Animals; Cells, Cultured; Glucose; Hypoglycemic Agents; Immunoblotting; Insulin; Insulin Resistance; Muscle Fibers, Skeletal; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rosiglitazone; Thiazolidinediones; Up-Regulation; Xanthenes; Xanthones | 2014 |
Norathyriol reverses obesity- and high-fat-diet-induced insulin resistance in mice through inhibition of PTP1B.
Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signalling. PTP1B deficiency improves obesity-induced insulin resistance and consequently improves type 2 diabetes in mice. Here, the small molecule norathyriol reversed obesity- and high-fat-diet-induced insulin resistance by inhibiting PTP1B.. The inhibitory mode of PTP1B was evaluated by using the double-reciprocal substrate in the presence of norathyriol. Primary cultured hepatocytes, myoblasts and white adipocytes were used to investigate the effect of norathyriol on insulin signalling. Glucose homeostasis and insulin sensitivity were characterised by glucose and insulin tolerance tests.. Norathyriol was identified as a competitive inhibitor of PTP1B, with an IC50 of 9.59 ± 0.39 μmol/l. In cultured hepatocytes and myoblasts, norathyriol treatment blocked the PTP1B-mediated dephosphorylation of the insulin receptor. Intraperitoneal injection of norathyriol inhibited liver and muscle PTP1B activity in mice, thus contributing to the improved glucose homeostasis and insulin sensitivity. However, these beneficial effects were abolished in PTP1B-deficient mice. Notably, oral administration of norathyriol protected mice from diet-induced obesity and insulin resistance through inhibition of hypothalamic PTP1B activity.. Our results indicate that the small molecule norathyriol is a potent PTP1B inhibitor with good cell permeability and oral availability. Topics: Animals; Blotting, Western; Diet, High-Fat; Immunoprecipitation; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Obesity; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Xanthenes | 2014 |