Skeletal muscle insulin resistance is known to play an important role in the pathogenesis of diabetes, and one potential causative cellular mechanism is endoplasmic reticulum (ER) stress. Adiponectin mediates anti-diabetic effects via direct metabolic actions and by improving insulin sensitivity, and we recently demonstrated an important role in stimulation of autophagy by adiponectin. However, there is limited knowledge on crosstalk between autophagy and ER stress in skeletal muscle and in particular how they are regulated by adiponectin. Here, we utilized the model of high insulin/glucose (HIHG)-induced insulin resistance, determined by measuring Akt phosphorylation (T308 and S473) and glucose uptake in L6 skeletal muscle cells. HIHG reduced autophagic flux measured by LC3 and p62 Western blotting and tandem fluorescent RFP/GFP-LC3 immunofluorescence (IF). HIHG also induced ER stress assessed by thioflavin T/KDEL IF, pIRE1, pPERK, peIF2α and ATF6 Western blotting and induction of a GRP78-mCherry reporter. Induction of autophagy by adiponectin or rapamycin attenuated HIHG-induced ER stress and improved insulin sensitivity. The functional significance of enhanced autophagy was validated by demonstrating a lack of improved insulin sensitivity in response to adiponectin in autophagy-deficient cells generated by overexpression of dominant negative mutant of Atg5. In summary, adiponectin-induced autophagy in skeletal muscle cells alleviated HIHG-induced ER stress and insulin resistance.
The purpose of this study was to examine the anti-oxidative activity of pectin and other polysaccharides in order to develop a cosmeceutical base having anti-oxidative effects towards retinyl palmitate (RP). The anti-oxidative stabilizing effects of pectin and other polysaccharides on RP were evaluated by DPPH assay and then the stabilizing effect of pectin on RP was examined as a function of time. Among the polysaccharides we examined, pectin exhibited a considerably higher anti-oxidative activity, with an approximately 5-fold greater DPPH radical scavenging effect compared to other polysaccharides. The DPPH radical scavenging effect of pectin increased gradually with increasing concentrations of pectin. At two different RP concentrations, 0.01 and 0.1% in ethanol, addition of pectin improved the stability of RP in a concentration dependent manner. The stabilizing effect of pectin on RP was more effective for the lower concentration of RP (0.01%, v/v). Further, degradation of RP was reduced following the addition of pectin as measured over 8 hours. From the results obtained, it can be suggested that pectin may be a promising ingredient for cosmeceutical bases designed to stabilize RP or other pharmacological agents subject to degradation by oxidation.
Celecoxib is a non-steroidal, anti-inflammatory drug used in the treatment of pain and inflammation associated with rheumatoid arthritis, and several other inflammatory disorders. It is a class II compound according to the Biopharmaceutics Classification System owing to its low water solubility and high membrane permeability. The objective of this study was to improve the solubility and dissolution rate of celecoxib using solid surfactant technology that might be useful in developing solid dosage forms. Solid surfactant was developed by mixing and grinding together a liquid surfactant (Tween 80) with various inorganic carriers like Fujicalin Ò (Dibasic Calcium Phosphate Anhydrous), Pineflow Ò (Porous-structured Maltodextrin), Neusilin Ò (Magnesium Alumino metasilicate) and Aerosil Ò (Colloidal Silicon dioxide) in a mortar and pestle in different ratios of liquid surfactant and the carrier to obtain solid surfactants. The celecoxib tablets prepared with solid surfactants were then evaluated for their solubility and dissolution properties. Among the fillers used, Fujicalin showed the highest solubilization capacity for celecoxib. The dissolution behaviors of various tablets prepared with solidified surfactants were compared to those of conventional celecoxib tablets in a simulated gastric fluid. Celecoxib tablets prepared using solidified surfactants showed improved dissolution behaviors when compared to the conventional counterparts. Fujicalin solidified Tween 80 was further analyzed by powder X-ray diffraction analysis, differential scanning calorimetry thermographs and reverse phase high performance liquid chromatography.
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