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A Western lifestyle with low physical activity and a diet rich in sugar, fat and processed food contribute to higher incidences of diabetes and obesity. Enhanced glucose uptake in human liver cells was observed after treatment with phenolic extracts from different Nordic berries. All berry extracts showed higher inhibition against α-amylase and α-glucosidase than the anti-diabetic agent acarbose. Total phenolic content and phenolic profiles in addition to antioxidant activities, were also investigated. The berries were extracted with 80% methanol on an accelerated solvent extraction system (ASE) and then purified by C-18 solid phase extraction (SPE). Among the ASE methanol extracts, black chokeberry, crowberry and elderberry extracts showed high stimulation of glucose uptake in HepG2 cells and also considerable inhibitory effect towards carbohydrate hydrolyzing enzymes. SPE extracts with higher concentrations of phenolics, resulted in increased glucose uptake and enhanced inhibition of α-amylase and α-glucosidase compared to the ASE extracts. Crowberry and cloudberry were the most potent 15-lipoxygenase inhibitors, while bog whortleberry and lingonberry were the most active xanthine oxidase inhibitors. These results increase the value of these berries as a component of a healthy Nordic diet and have a potential benefit against diabetes. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is manifested by progressive metabolic impairments in tissues such as skeletal muscle and liver, and these tissues become less responsive to insulin, leading to hyperglycemia. In the present study, stimulation of glucose and oleic acid uptake by elderflower extracts, constituents and metabolites were tested in vitro using the HepG2 hepatocellular liver carcinoma cell line and human skeletal muscle cells. Among the crude extracts, the 96% EtOH extract showed the highest increase in glucose and oleic acid uptake in human skeletal muscle cells and HepG2-cells. The flavonoids and phenolic acids contained therein were potent stimulators of glucose and fatty acid uptake in a dose-dependent manner. Most of the phenolic constituents and several of the metabolites showed high antioxidant activity and showed considerably higher α-amylase and α-glucosidase inhibition than acarbose. Elderflower might therefore be valuable as a functional food against diabetes. [ABSTRACT FROM AUTHOR]

Background and Aims: Physical exercise leads to substantial adaptive responses in skeletal muscles and plays a central role in a healthy life style. Since exercise induces major systemic responses, underlying cellular mechanisms are difficult to study in vivo. It was therefore desirable to develop an in vitro model that would resemble training in cultured human myotubes. Methods: Electrical pulse stimulation (EPS) was applied to adherent human myotubes. Cellular contents of ATP, phosphocreatine (PCr) and lactate were determined. Glucose and oleic acid metabolism were studied using radio-labeled substrates, and gene expression was analyzed using real-time RT-PCR. Mitochondrial content and function were measured by live imaging and determination of citrate synthase activity, respectively. Protein expression was assessed by electrophoresis and immunoblotting. Results: High-frequency, acute EPS increased deoxyglucose uptake and lactate production, while cell contents of both ATP and PCr decreased. Chronic, low-frequency EPS increased oxidative capacity of cultured myotubes by increasing glucose metabolism (uptake and oxidation) and complete fatty acid oxidation. mRNA expression level of pyruvate dehydrogenase complex 4 (PDK4) was significantly increased in EPS-treated cells, while mRNA expressions of interleukin 6 (IL-6), cytochrome C and carnitin palmitoyl transferase b (CPT1b) also tended to increase. Intensity of MitoTrackerHRed FM was doubled after 48 h of chronic, low-frequency EPS. Protein expression of a slow fiber type marker (MHCI) was increased in EPS-treated cells. Conclusions: Our results imply that in vitro EPS (acute, high-frequent as well as chronic, low-frequent) of human myotubes may be used to study effects of exercise. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is manifested by progressive metabolic impairments in tissues such as skeletal muscle and liver, and these tissues become less responsive to insulin, leading to hyperglycemia. In the present study, stimulation of glucose and oleic acid uptake by elderflower extracts, constituents and metabolites were tested in vitro using the HepG2 hepatocellular liver carcinoma cell line and human skeletal muscle cells. Among the crude extracts, the 96% EtOH extract showed the highest increase in glucose and oleic acid uptake in human skeletal muscle cells and HepG2-cells. The flavonoids and phenolic acids contained therein were potent stimulators of glucose and fatty acid uptake in a dose-dependent manner. Most of the phenolic constituents and several of the metabolites showed high antioxidant activity and showed considerably higher α-amylase and α-glucosidase inhibition than acarbose. Elderflower might therefore be valuable as a functional food against diabetes.

The nuclear liver X receptors (LXRalpha and beta) are regulators of lipid and cholesterol metabolism. Oxysterols are known LXR ligands, but the functional role of hydroxycholesterols is at present unknown. In human myotubes, chronic exposure to the LXR ligand T0901317 promoted formation of diacylglycerol (DAG) and triacylglycerol (TAG), 22-R-hydroxycholesterol (22-R-HC) had no effect, and 22-S-hydroxycholesterol (22-S-HC) reduced the formation. In accordance with this, 22-HC and T0901317 regulated the expression of fatty acid transporter CD36, stearoyl-CoA desaturase-1, acyl-CoA synthetase long chain family member 1 and fatty acid synthase (FAS) differently; all genes were increased by T0901317, 22-R-HC did not change their expression level, while 22-S-HC reduced it. Transfection studies confirmed that the FAS promoter was activated by T0901317 and repressed by 22-S-HC through an LXR response element in the promoter. Both 22-R-HC and T0901317 increased gene expression of LXRalpha, sterol regulatory element-binding protein 1c and ATP-binding cassette transporter A1, while 22-S-HC had little effect. In summary, 22-R-HC regulated lipid metabolism and mRNA expression of some LXR target genes in human myotubes differently than T0901317. Moreover, 22-S-HC did not behave like an inactive ligand; it reduced synthesis of complex lipids and repressed certain genes involved in lipogenesis and lipid handling.

The effect of changes in microsomal incubation conditions (NADPH, Mg(2+), Cl(-), NADPH-regenerating system and pH) on the formation of the CYP3A4 metabolites AM1 and AM9 from CsA were studied by application of a fractional factorial design. Metabolism was studied in microsomes of transfected human liver epithelial (THLE) cells specifically expressing CYP3A4. Within the conditions tested, a 3-4-fold difference in formation of CsA metabolites was observed. Formation of both AM1 and AM9 was favoured by a low Mg(2+) concentration (0.5 mM) and no addition of Cl(-) to the incubation matrix. However, while a high NADPH concentration (1.75 mM) was the single most important factor for the formation of AM1, changes in NADPH concentration between 0.25 and 1.75 mM had no influence on AM9 formation. Formation of the two metabolites also differed in their influence by pH changes, as a change in pH from 7.2 to 7.5 significantly increased the formation of AM9, while formation of AM1 was unaffected by this change. The present study showed that relatively small changes in the incubation matrix had a significant influence on the microsomal CYP3A4-mediated metabolism of CsA. Systematic studies on microsomal incubation conditions could be a key to improve metabolic in vitro-in vivo extrapolations in drug development.