Glucose Uptake Activity Research Articles

Study of glucose uptake enhancing potential of fenugreek (Trigonella foenum graecum) leaves extract on 3T3 L1 cells line and evaluation of its antioxidant potential

Background: The incidence of diabetes mellitus (DM) is increasing at an alarming rate globally. There is a need for suitable natural alternatives for its treatment, as the regular use of drugs causes several secondary health issues. Aim: This study aimed to quantitatively evaluate the phenol and flavonoid content; antioxidant and anti-diabetic activity of fenugreek seeds and leaves in water and ethanolic extracts. Materials and Methods: Dried and powdered seeds and leaves of fenugreek were treated at different time and temperature combinations (100°C for 10 min; 80°C for 30 min; 60°C for 1 h; 37°C for 6 h; 24°C [room temperature] for 24 h; 100°C for 10 min followed by overnight soaking). Total phenolic content, total flavonoid content, 2,2-Diphenyl-1-picrylhydrazyl (DPPH), and glucose uptake assays on 3T3-L1 cell lines were performed on the extracts. Results: The results show that fenugreek leaves treated at 100°C for 10 min and overnight soaking yield extracts with the highest concentrations of desired phenols (46.08 ± 0.15 mg GAE/g sample) and flavonoid content (13.02 ± 0.44 mg/g sample) and antioxidant activity (DPPH) (45.41 ± 2.1%) with enhanced glucose uptake activity in 3T3-L1 cell lines. Conclusion: The phenolic and flavonoid content, DPPH radical scavenging activity and antidiabetic activity was highest in the water extract of fenugreek leaves treated at 100°C for 10 min and subsequent soaking for 24 h before filtration as compared to the other protocols tested. Furthermore, water extracts showed enhanced activity as compared to the ethanol extracts in case of both seeds and leaves and in all the treatment combinations. Abbreviations Used: 2NBDG: (2-(N-(7-Nitrobenz-2-oxa-1, 3-diazol-4-yl) Amino)-2-Deoxyglucose), DM: Diabetes mellitus, DMEM: Dulbecco's Modified Eagle's Medium, DPPH: 2,2-Diphenyl-1-picrylhydrazyl, GA: Gallic Acid, GAE: Gallic Acid Equivalents, PBS: Phosphate Buffered Saline, TFC: Total Flavonoid Content, TPC: Total Phenolic Content

Polyphenols and their effects on diabetes management: A review.

Background: Type 2 diabetes is a growing public health problem and is associated with increased morbidity and mortality. The worldwide prevalence of type 2 diabetes is rising. Polyphenols, such as flavonoids, phenolic acid, and stilbens, are a large and heterogeneous group of phytochemicals in plant-based foods. In this review, we aimed at assessing the studies on polyphenols and diabetes management. Methods: A literature search in the PubMed, EMBASE, Scopus, and ISI Web of Science databases was conducted to identify relevant studies published from 1986 to Jan 2017. Results: Several animal models and a limited number of human studies have revealed that polyphenols decrease hyperglycemia and improve acute insulin secretion and insulin sensitivity. The possible mechanisms include decrease in glucose absorption in the intestine, inhibition of carbohydrates digestion, stimulation of insulin secretion, modulation of glucose release from the liver, activation of insulin receptors and glucose uptake in insulin-sensitive tissues, modulation of intracellular signaling pathways, and gene expression. Conclusion: Growing evidence indicates that various dietary polyphenols may influence blood glucose at different levels and may also help control and prevent diabetes complication. However, we still need more clinical trials to determine the effects of polyphenols- rich foods, their effective dose, and mechanisms of their effects in managing diabetes.

Potential for subsets of wt-NPM1 primary AML blasts to respond to retinoic acid treatment.

Acute myeloid leukemia (AML) has high mortality rates, perhaps reflecting a lack of understanding of the molecular diversity in various subtypes and a lack of known actionable targets. There are currently 12 open clinical trials for AML using combination therapeutic modalities including all-trans retinoic acid (RA). Mutant nucleophosmin-1, proposed as a possible marker for RA response, is the criterion for recruiting patients in three active RA phase 3 clinical trials. We tested the ability of RA alone or in combination with either bosutinib (B) or 6-formylindolo(3,2-b) carbazole (F) to induce conversion of 12 de novo AML samples toward a more differentiated phenotype. We assessed levels of expression of cell surface markers associated with differentiation, aldehyde dehydrogenase activity, and glucose uptake activity. Colony formation capacity was reduced with the combined treatment of RA and B or F, and correlated with modulation of a c-Cbl/Lyn/c-Raf-centered signalsome. Combination treatment was in most cases more effective than RA alone. Based on their responses to the treatments, some primary leukemic samples cluster closer to HL-60 cells than to other primary samples, suggesting that they may represent a hitherto undefined AML subtype that is potentially responsive to RA in a combination differentiation therapy.

A role for Candida albicans superoxide dismutase enzymes in glucose signaling

The Saccharomyces cerevisiae and Candida albicans yeasts have evolved to differentially use glucose for fermentation versus respiration. S. cerevisiae is Crabtree positive, where glucose represses respiration and promotes fermentation, while the opportunistic fungal pathogen C. albicans is Crabtree negative and does not repress respiration with glucose. We have previously shown that glucose control in S. cerevisiae involves the antioxidant enzyme Cu/Zn superoxide dismutase (SOD1), where H2O2 generated by SOD1 stabilizes the casein kinase YCK1 for glucose sensing. We now demonstrate that C. albicans SODs also participate in glucose regulation. C. albicans expresses two cytosolic SODs, Cu/Zn SOD1 and Mn containing SOD3, and both complemented a S. cerevisiae sod1Δ mutant in stabilizing YCK1. Moreover, in C. albicans cells, both SODs functioned to repress glucose transporter genes in response to glucose. However, the action of SODs in glucose control has diverged in the two yeasts. In S. cerevisiae, SOD1 specifically functions in the glucose sensing pathway involving YCK1 and the RGT1 repressor, but the analogous YCK/RGT1 pathway in C. albicans shows no control by SOD enzymes. Instead C. albicans SODs work in the glucose repression pathway involving the MIG1 transcriptional repressor. In C. albicans, the SODs repress glucose uptake, while in S. cerevisiae, SOD1 activates glucose uptake, in accordance with the divergent modes for glucose utilization in these two distantly related yeasts.

Ecm33 is a novel factor involved in efficient glucose uptake for nutrition‐responsive TORC1 signaling in yeast

Glucose uptake is crucial for providing both an energy source and a signal that regulates cell proliferation. Therefore, it is important to clarify the mechanisms underlying glucose uptake and its transmission to intracellular signaling pathways. In this study, we searched for a novel regulatory factor involved in glucose-induced signaling by using Saccharomyces cerevisiae as a eukaryotic model. Requirement of the extracellular protein Ecm33 in efficient glucose uptake and full activation of the nutrient-responsive TOR kinase complex 1 (TORC1) signaling pathway is shown. Cells lacking Ecm33 elicit a series of starvation-induced pathways even in the presence of extracellular high glucose concentration. This results in delayed cell proliferation, reduced ATP, induction of autophagy, and dephosphorylation of the TORC1 substrates Atg13 and Sch9.

Hypoglycemic effect of <i>Berberis microphylla</i> G Forst root extract

Purpose: To evaluate the effect of the root extract of Berberis microphylla on glucose uptake and AMPK-activated protein kinase (AMPK) activity in non-resistant and insulin-resistant HepG2 cells. Methods: B. microphylla root was extracted with absolute ethanol, filtered, concentrated and lyophilized. Subsequently, liver cells, HepG2 (resistant and non-insulin resistant), were exposed for 24 h to different concentrations of the extract (10, 5, 2.5 and 1.25 x 10 -3 μg/μL) to determine the stimulation of glucose uptake and phosphorylation of AMPK. Results: In HepG2 cells without resistance exposed to B. microphylla root extract, glucose uptake varied from 34 to 59 % of the available glucose while AMPK phosphorylation was 1.9 to 3.6 times the phosphorylation of the control. In insulin-resistant HepG2 cells, glucose uptake varied from 68 to 95 % of available glucose while AMPK phosphorylation was 1.8 to 3.3 times the phosphorylation of the control. Conclusion: The root extract o f B. microphylla possesses hypoglycemic effects and stimulates glucose uptake in HepG2 cells with and without resistance by activating AMPK protein. Keywords: Calafate, Diabetes, Antihyperglycemic effect, Phytomedicine, Berberis, Insulin resistance

Flavonoids from Tetracera indica Merr. induce adipogenesis and exert glucose uptake activities in 3T3-L1 adipocyte cells

BackgroundTetracera indica Merr. (Family: Dilleniaceae), known to the Malay as ‘Mempelas paya’, is one of the medicinal plants used in the treatment of diabetes in Malaysia. However, no proper scientific study has been carried out to verify the traditional claim of T. indica as an antidiabetic agent. Hence, the aims of the present study were to determine the in vitro antidiabetic potential of the T. indica stems ethanol extract, subfractions and isolated compounds.MethodsThe ethanol extract and its subfractions, and isolated compounds from T. indica stems were subjected to cytotoxicity test using MTT viability assay on 3T3-L1 pre-adipocytes. Then, the test groups were subjected to the in vitro antidiabetic investigation using 3T3-L1 pre-adipocytes and differentiated adipocytes to determine the insulin-like and insulin sensitizing activities. Rosiglitazone was used as a standard antidiabetic agent. All compounds were also subjected to fluorescence glucose (2-NBDG) uptake test on differentiated adipocytes. Test solutions were introduced to the cells in different safe concentrations as well as in different adipogenic cocktails, which were modified by the addition of compounds to be investigated and in the presence or absence of insulin. Isolation of bioactive compounds from the most effective subfraction (ethyl acetate) was performed through repeated silica gel and sephadex LH-20 column chromatographies and their structures were elucidated through 1H–and 13C–NMR spectroscopy.ResultsFour monoflavonoids, namely, wogonin, norwogonin, quercetin and techtochrysin were isolated from the T. indica stems ethanol extract. Wogonin, norwogonin and techtochrysin induced significant (P < 0.05) adipogenesis like insulin and enhanced adipogenesis like rosiglitazone. Wogonin and norwogonin also exhibited significant (P < 0.05) glucose uptake activity.ConclusionThe present study demonstrated that the flavonoids isolated from the T. indica stems possess antidiabetic potential revealing insulin-like and insulin-sensitizing effects which were significant among the compounds. This also rationalizes the traditional use of T. indica in the management of diabetes in Malaysia.

Nuclear factor E2-related factor-2 has a differential impact on MCT1 and MCT4 lactate carrier expression in colonic epithelial cells: a condition favoring metabolic symbiosis between colorectal cancer and stromal cells.

Malignant tumors, such as colorectal cancer (CRC), are heterogeneous diseases characterized by distinct metabolic phenotypes. These include Warburg- and reverse Warburg phenotypes depending on differential distribution of the lactate carrier proteins monocarboxylate transporter-4 and -1 (MCT4 and MCT1). Here, we elucidated the role of the antioxidant transcription factor nuclear factor E2-related factor-2 (Nrf2) as the key regulator of cellular adaptation to inflammatory/environmental stress in shaping the metabolism toward a reverse Warburg phenotype in malignant and premalignant colonic epithelial cells. Immunohistochemistry of human CRC tissues revealed reciprocal expression of MCT1 and MCT4 in carcinoma and stroma cells, respectively, accompanied by strong epithelial Nrf2 activation. In colorectal tissue from inflammatory bowel disease patients, MCT1 and Nrf2 were coexpressed as well, relating to CD68+inflammatory infiltrates. Indirect coculture of human NCM460 colonocytes with M1- but not M2 macrophages induces MCT1 as well as G6PD, LDHB and TALDO expression, whereas MCT4 expression was decreased. Nrf2 knockdown or reactive oxygen species (ROS) scavenging blocked these coculture effects in NCM460 cells. Likewise, Nrf2 knockdown inhibited similar effects of tBHQ-mediated Nrf2 activation on NCM460 and HCT15 CRC cells. M1 coculture or Nrf2 activation/overexpression greatly altered the lactate uptake but not glucose uptake and mitochondrial activities in these cells, reflecting the reverse Warburg phenotype. Depending on MCT1-mediated lactate uptake, Nrf2 conferred protection from TRAIL-induced apoptosis in NCM460 and HCT15 cells. Moreover, metabolism-dependent clonal growth of HCT15 cells was induced by Nrf2-dependent activation of MCT1-driven lactate exchange. These findings indicate that Nrf2 has an impact on the metabolism already in premalignant colonic epithelial cells exposed to inflammatory M1 macrophages, an effect accompanied by growth and survival alterations. Favoring the reverse Warburg effect, these Nrf2-dependent alterations add to malignant transformation of the colonic epithelium.

In vitro contraction protects against palmitate-induced insulin resistance in C2C12 myotubes.

We are interested in understanding mechanisms that govern the protective role of exercise against lipid-induced insulin resistance, a key driver of type 2 diabetes. In this context, cell culture models provide a level of abstraction that aid in our understanding of cellular physiology. Here we describe the development of an in vitro myotube contraction system that provides this protective effect, and which we have harnessed to investigate lipid-induced insulin resistance. C2C12 myocytes were differentiated into contractile myotubes. A custom manufactured platinum electrode system and pulse stimulator, with polarity switching, provided an electrical pulse stimulus (EPS) (1 Hz, 6-ms pulse width, 1.5 V/mm, 16 h). Contractility was assessed by optical flow flied spot noise mapping and inhibited by application of ammonium acetate. Following EPS, myotubes were challenged with 0.5 mM palmitate for 4 h. Cells were then treated with or without insulin for glucose uptake (30 min), secondary insulin signaling activation (10 min), and phosphoinositide 3-kinase-α (PI3Kα) activity (5 min). Prolonged EPS increased non-insulin-stimulated glucose uptake (83%, P = 0.002), Akt (Thr308) phosphorylation (P = 0.005), and insulin receptor substrate-1 (IRS-1)-associated PI3Kα activity (P = 0.048). Palmitate reduced insulin-specific action on glucose uptake (-49%, P < 0.001) and inhibited insulin-stimulated Akt phosphorylation (P = 0.049) and whole cell PI3Kα activity (P = 0.009). The inhibitory effects of palmitate were completely absent with EPS pretreatment at the levels of glucose uptake, insulin responsiveness, Akt phosphorylation, and whole cell PI3Kα activity. This model suggests that muscle contraction alone is a sufficient stimulus to protect against lipid-induced insulin resistance as evidenced by changes in the proximal canonical insulin-signaling pathway.

Improvement of mitochondrial function by celastrol in palmitate-treated C2C12 myotubes via activation of PI3K-Akt signaling pathway

Compelling evidences posited that high level of saturated fatty acid gives rise to mitochondrial dysfunction and inflammation in the development of insulin resistance in skeletal muscle. Celastrol is a pentacyclic triterpenoid derived from the root extracts of Tripterygium wilfordii that possesses potent anti-inflammatory properties in a number of animal models with metabolic diseases. However, the cellular mechanistic action of celastrol in alleviating obesity-induced insulin resistance in skeletal muscle remains largely unknown. Therefore, the present investigation evaluated the attributive properties of celastrol at different concentrations (10, 20, 30 and 40nM) on insulin resistance in C2C12 myotubes evoked by palmitate. We demonstrated that celastrol improved mitochondrial functions through significant enhancement of intracellular ATP content, mitochondrial membrane potential, citrate synthase activity and decrease of mitochondrial superoxide productions. Meanwhile, augmented mitochondrial DNA (mtDNA) content with suppressed DNA oxidative damage were observed following celastrol treatment. Celastrol significantly enhanced fatty acid oxidation rate and increased the level of tricarboxylic acid (TCA) cycle intermediates in palmitate-treated cells. Further analysis revealed that the improvement of glucose uptake activity in palmitate-loaded myotubes was partly mediated by celastrol via activation of PI3K-Akt insulin signaling pathway. Collectively, these findings provided evidence for the first time that the protection from palmitate-mediated insulin resistance in C2C12 myotubes by celastrol is likely associated with the improvement of mitochondrial functions-related metabolic activities.

Do diabetes and obesity affect the metabolic response to exercise?

Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. Poor glycemic control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent on the glucagon/insulin ratio and the exercise-induced increase in hepatokines such as fibroblast growth factor 21 and follistatin is impaired in type 2 diabetes and obesity, but consequences for the benefit from exercise are unknown yet. Severe metabolic dysregulation can reduce the benefit from exercise, but the intact response of key metabolic regulators in exercising skeletal muscle of diabetic patients demonstrates the effectiveness of exercise programs to treat the disease.

Abstract 1157: Screening and identification of new generation glucose transporter inhibitors as anticancer therapeutics

Abstract Cancer is a top killer second only to cardiovascular diseases. Cellular metabolic reprogramming and altered energetics are key features of cancer. Opportunistic uptake of extracellular nutrients has recently been named as an emerging hallmark of cancer metabolism. Glucose is a key nutrient taken in by cancer cells for satisfying their high energy and biosynthesis needs. Drastic upregulation of glucose uptake and glycolytic activity, a phenomenon called the Warburg effect, is prevalent in cancers. Cancer cells overexpress specific glucose transporters (Gluts), particularly Glut1, on cell membranes for taking in glucose via facilitated diffusion. Considering the addiction of cancer cells for glucose and their sensitivity and vulnerability to changes in glucose supply, Gluts, especially Glut1, have been recognized as an attractive anticancer target. We previously reported the identification of first generation lead Glut1 inhibitor WZB117 (1). WZB117 treatment of human nonsmall cell lung cancer (NSCLC) A549 cells resulted in inhibition of glucose uptake, glycolysis and induction of apoptosis and necrosis. In addition, WZB-117 reduced tumor growth by ~70% in an A549 tumor mouse model. WZB117 inhibit cell growth of 7 cancer cell lines in 4 cancer types with IC50 values lower than 10 μM. Through a structure activity relationship (SAR) study of WZB117, a second generation lead, DRB18, has been identified. DRB-18 is much more stable and 5 to 10 times more potent than WZB117 in inhibiting growth and proliferation in about 90% of the 60 different cancer cell lines in 9 major cancer types as revealed in NCI-60 screenings. And its IC50s in many cancer cell lines are in the high nM range. In this study, we also report new compounds screening results for the objective of identifying novel compounds with higher glucose transport-inhibitory and cancer cell growth-inhibitory activities using nonsmall cell lung cancer cell lines as models.

Pterostilbene Inhibits Lipogenic Activity similar to Resveratrol or Caffeine but Differently Modulates Lipolysis in Adipocytes.

The anti-obesity effects of resveratrol shown in rodents are not transposed into an efficient therapy of human obesity. Consequently, the search for molecules mimicking or surpassing resveratrol actions is ongoing. The natural phenolic compound pterostilbene exhibits beneficial health effects and has the capacity to limit fat mass in animal models. In this study, we tested whether pterostilbene modulates triacylglycerol accumulation/breakdown. Prolonged exposure to pterostilbene or resveratrol inhibited adipocyte differentiation in 3T3-F442A preadipocytes. Acute effects on lipolysis, antilipolysis and lipogenesis were determined for pterostilbene in mouse adipocytes, and compared with resveratrol. Pterostilbene was also tested on glycerol release and glucose uptake in subcutaneous human adipocytes. Dose-response analyses did not reveal a clear lipolytic effect in both species. The antilipolytic effect of insulin was improved by pterostilbene at 1-10μM in mouse fat cells only, while at 1mM, the phenolic compound was antilipolytic in human fat cells in a manner not additive to insulin. Pterostilbene dose-dependently inhibited glucose incorporation into lipids similarly to resveratrol and caffeine. However, only the former did not inhibit insulin-stimulated glucose uptake. Indeed, pterostilbene abolished the insulin lipogenic effect without inhibiting its antilipolytic action and rapid activation of glucose uptake. Pterostilbene therefore exhibits a unique panel of direct interactions with adipocytes that relies on its reported anti-obesity and antidiabetic properties. Copyright © 2017 John Wiley & Sons, Ltd.

In vitro production of insulin-responsive skeletal muscle tissue from mouse embryonic stem cells by spermine-induced differentiation method.

The treatment of an embryoid body with spermine for a short duration can trigger the generation of a 3-dimensional multilayer myotube sheet (MMTS) that shows pulsatile activity. MMTS was previously characterized as a model of skeletal muscle tissue. In the present work, the insulin responsiveness of MMTS was investigated because it is an essential function for a model of skeletal muscle. The glucose uptake activity of MMTS was analyzed by confocal microscopy using fluorescent glucose analogs, namely 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG) and its L-glucose counterpart, 2-NBDLG. The specific uptake rate of glucose was estimated from the difference between the fluorescent signals of 2-NBDG and 2-NBDLG. It was enhanced by insulin stimulation to 3.6 times higher than the control without insulin, and this insulin responsiveness was maintained for 5days. The advantages of the 3-dimensional structure of MMTS are discussed in the contexts of its potential in vivo and in vitro uses.

Metabolic Investigations of the Molecular Mechanisms Associated with Parkinson's Disease.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by fibrillar cytoplasmic aggregates of α-synuclein (i.e., Lewy bodies) and the associated loss of dopaminergic cells in the substantia nigra. Mutations in genes such as α-synuclein (SNCA) account for only 10% of PD occurrences. Exposure to environmental toxicants including pesticides and metals (e.g., paraquat (PQ) and manganese (Mn)) is also recognized as an important PD risk factor. Thus, aging, genetic alterations, and environmental factors all contribute to the etiology of PD. In fact, both genetic and environmental factors are thought to interact in the promotion of idiopathic PD, but the mechanisms involved are still unclear. In this study, we summarize our findings to date regarding the toxic synergistic effect between α-synuclein and paraquat treatment. We identified an essential role for central carbon (glucose) metabolism in dopaminergic cell death induced by paraquat treatment that is enhanced by the overexpression of α-synuclein. PQ “hijacks” the pentose phosphate pathway (PPP) to increase NADPH reducing equivalents and stimulate paraquat redox cycling, oxidative stress, and cell death. PQ also stimulated an increase in glucose uptake, the translocation of glucose transporters to the plasma membrane, and AMP-activated protein kinase (AMPK) activation. The overexpression of α-synuclein further stimulated an increase in glucose uptake and AMPK activity, but impaired glucose metabolism, likely directing additional carbon to the PPP to supply paraquat redox cycling.

Identification of molecular pathways affected by treatment with heartwood water extract of Pterocarpus marsupium in MCF 7 cancer cell line

The heartwood of Pterocarpus marsupium Roxb. has a history of traditional use in Ayurveda and traditional systems of medicines for the management of conditions such as diabetes and hyperlipidemia. The present study was conducted to identify the molecular pathways affected by a Heartwood Water Extract of P. marsupium (HWE). The effects of HWE on glucose uptake, as well as anti-oxidant and cytotoxic potential were studied in C2C12 and MCF-7 cell lines. An MCF-7 cell line synthesizing cholesterol and cholic acid, which generally occurs in liver cells, was treated with HWE and used to explicate the affected pathways through metabolomics.The study showed that treatment with HWE (100μg/mL) significantly increased antioxidant enzyme activity and increased glucose uptake activity by >3.0 fold (P<0.05). Treatment of MCF-7 cells with HWE (10mg/mL), also showed statistically significant apoptotic effects, with 78.2±2.4% (P<0.01) apoptotic cells at 24h. Metabolomics showed 36 metabolites to be differentially expressed to a significant degree after treatment with HWE. Amongst these, cholesterol synthesis intermediates, cholic acid derivatives, coenzyme A and sphingolipids were down-regulated (≥2 fold; P<0.05) in the HWE treated cell line. Histamine and carotene were found to be up-regulated by >2 fold. Nine pathways were found to be differentially regulated by HWE treatment, and cholic acid and sphingolipid pathways were identified as the primary targets of HWE.Decreased synthesis of cholic acid derivatives leads to less buffering and reduced absorption of lipids. The data suggests that reduced coenzyme A and increased histamine levels activated H+/K+ ATPase and that the resultant increase in energy consumption led the cells to apoptosis. The results also indicate that HWE regulates lipid and glucose homeostasis and suggest that HWE has a multi-faceted potential in the amelioration of hyperlipidemia and diabetes, as well as potential applications in cancer treatment.

In vitro cytotoxicity and glucose uptake activity of chrysin, a flavone in l6 cell lines

In vitro cytotoxicity and glucose uptake activity of chrysin, a flavone in l6 cell lines

Metaformin-Based Regimen Inhibits Glucose Uptake and G6PD Activity: A de novo Anti-cervical Cancer Strategy Tackles HeLa and its Derivative Hep2 Cells

Metaformin-Based Regimen Inhibits Glucose Uptake and G6PD Activity: A de novo Anti-cervical Cancer Strategy Tackles HeLa and its Derivative Hep2 Cells

Phenolic compounds isolated from fermented blueberry juice decrease hepatocellular glucose output and enhance muscle glucose uptake in cultured murine and human cells

BackgroundWe recently reported that blueberry juice fermented (FJ) with Serratia vaccinii bacterium has antidiabetic activities both in vivo and in vitro. The purpose of this project was to elucidate the effect of FJ on glucose homeostasis in liver and skeletal muscle cells and to identify active fractions/compounds responsible for this effect.MethodsFJ was fractionated using standard chromatography procedures. Hepatic (H4IIE, HepG2) and skeletal muscle cells (C2C12) were treated with maximum non-toxic concentrations of FJ, fractions and isolated compounds thereof. Glucose-6-phosphatase (G6Pase) activity was measured using glucose oxidase method. To measure glucose uptake and glycogen synthase (GS) activity, radioactive assays were used.ResultsFractionation of FJ yielded seven fractions. FJ and its phenolic fractions F2, F3-1 and F3-2 respectively inhibited G-6Pase by 31, 45, 51 and 26%; activated GS by 2.3-, 2.3-, 2.2- and 2-fold; and stimulated glucose uptake by 19, 25, 18 and 15%, as compared to DMSO vehicle control. Subfractionation of the active fractions yielded 4 compounds (catechol, chlorogenic, gallic and protocatechuic acid). Catechol, yielding the greatest bioactivity in G6Pase and glucose uptake assays, decreased G6Pase activity by 54%, increased GS by 2-fold and stimulated glucose uptake by 44% at 45.5 μM.ConclusionsThis study identifies novel potential antidiabetic compounds that can help standardize FJ.

Fabrication, characterization, in vitro drug release and glucose uptake activity of 14-deoxy, 11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles

Biodegradable polymer based novel drug delivery systems brought a considerable attention in enhancing the therapeutic efficacy and bioavailability of various drugs. 14-deoxy 11, 12-didehydro andrographolide (poorly water soluble compound) loaded polycaprolactone (nano-DDA) was synthesized using the solvent evaporation technique. Nano-DDA was characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS) studies. Fourier Transform InfraRed Spectroscopy (FTIR) was used to investigate the structural interaction between the drug and the polymer. Functional characterization of the formulation was determined using drug content, cellular uptake and in vitro drug release. 2-deoxy-D-[1-3H] glucose uptake assay was carried out to assess the antidiabetic potential of nano-DDA in L6 myotubes. The nano-DDA displayed spherical shape with a smooth surface (252.898 nm diameter), zeta potential, encapsulation and loading efficiencies of −38.9 mV, 91.98 ± 0.13% and 15.09 ± 0.18% respectively. No structural alteration between the drug and the polymer was evidenced (FTIR analysis). Confocal microscopy studies with rhodamine 123 loaded polycaprolactone nanoparticles (Rh123-PCL NPs) revealed the internalization of Rh123-PCL NPs in a time dependent manner in L6 myoblasts. A dose dependent increase in glucose uptake was observed for nano-DDA with a maximal uptake of 108.54 ± 1.42% at 100 nM on L6 myotubes, thereby proving its anti-diabetic efficacy. A biphasic pattern of in vitro drug release demonstrated an initial burst release at 24 h followed by a sustained release for up to 11 days. To conclude, our results revealed that nano-DDA formulation can be a potent candidate for antidiabetic drug delivery.