Large Amounts Of Glucose Research Articles

Metabolic and transcriptomic analyses of nectaries reveal differences in the mechanism of nectar production between monocots (Ananas comosus) and dicots (Nicotiana tabacum)

BackgroundNectar is offered by numerous flowering plants to attract pollinators. To date, the production and secretion of nectar have been analyzed mainly in eudicots, particularly rosids such as Arabidopsis. However, due to the enormous diversity of flowering plants, further research on other plant species, especially monocots, is needed. Ananas comosus (monocot) is an economically important species that is ideal for such analyses because it produces easily accessible nectar in sufficient quantities. In addition, the analyses were also carried out with Nicotiana tabacum (dicot, asterids) for comparison.ResultsWe performed transcriptome sequencing (RNA-Seq) analyses of the nectaries of Ananas comosus and Nicotiana tabacum, to test whether the mechanisms described for nectar production and secretion in Arabidopsis are also present in these plant species. The focus of these analyses is on carbohydrate metabolism and transport (e.g., sucrose-phosphate synthases, invertases, sucrose synthases, SWEETs and further sugar transporters). In addition, the metabolites were analyzed in the nectar, nectaries and leaves of both plant species to address the question of whether concentration gradients for different metabolites exist between the nectaries and nectar The nectar of N. tabacum contains large amounts of glucose, fructose and sucrose, and the sucrose concentration in the nectar appears to be similar to the sucrose concentration in the nectaries. Nectar production and secretion in this species closely resemble corresponding processes in some other dicots, including sucrose synthesis in nectaries and sucrose secretion by SWEET9. The nectar of A. comosus also contains large amounts of glucose, fructose and sucrose and in this species the sucrose concentration in the nectar appears to be higher than the sucrose concentration in the nectaries. Furthermore, orthologs of SWEET9 generally appear to be absent in A. comosus and other monocots. Therefore, sucrose export by SWEETs from nectaries into nectar can be excluded; rather, other mechanisms, such as active sugar export or exocytosis, are more likely.ConclusionThe mechanisms of nectar production and secretion in N. tabacum appear to be largely similar to those in other dicots, whereas in the monocotyledonous species A. comosus, different synthesis and transport processes are involved.

Inhibition of the mitochondrial respiratory chain reduces catecholamine‑stimulated lipolysis via increasing lactate production in 3T3‑L1 adipocytes.

Adipose tissue serves a significant role in the regulation of energy metabolism in the body. The re‑esterification of the fatty acids generated during lipolysis is critical for efficient lipolysis. However, the effect of the intracellular energy state on lipolytic activity and fatty acid re‑esterification during lipolysis is not yet fully understood. The present study aimed to assess the effect of the intracellular energy state on lipolytic activity and fatty acid re‑esterification during lipolysis. 3T3‑L1 adipocytes were incubated with mitochondrial respiratory chain inhibitors, oligomycin A or rotenone, during isoproterenol stimulation; and glycerol, glucose and lactate concentrations in the medium were measured. Western blot analysis was performed to examine the phosphorylation levels of cAMP‑dependent protein kinase A (PKA). The results showed that inhibition of mitochondrial ATP synthesis decreased catecholamine‑stimulated lipolysis without affecting PKA signaling. The inhibition of mitochondrial respiration increased glucose uptake and lactate production, indicating that a large amount of glucose taken up into the cell was preferentially used for ATP production rather than for re‑esterification. In conclusion, the results of the present study suggested that the energy state during lipolysis may influence lipolytic activity by suppressing fatty acid re‑esterification.

Regulatory mechanisms of glucose absorption in the mouse proximal small intestine during fasting and feeding

Fasting is known to alter the function of various organs and the mechanisms of glucose metabolism, which affect health outcomes and slow aging. However, it remains unclear how fasting and feeding affects glucose absorption function in the small intestine. We studied the effects of the fasting and feeding on glucose-induced short-circuit current (Isc) in vitro using an Ussing chamber technique. Glucose-induced Isc by SGLT1 was observed in the ileum, but little or no Isc was observed in the jejunum in ad libitum-fed mice. However, in mice fasted for 24–48 h, in addition to the ileum, robust glucose-induced Isc was observed over time in the jejunum. The expression of SGLT1 in the brush border membranes was significantly decreased in the jejunum under fed conditions compared to 48 h fasting, as analyzed by western blotting. Additionally, when mice were fed a 60% high glucose diet for 3 days, the increase in glucose-induced Isc was observed only in the ileum, and totally suppressed in the jejunum. An increase in Na+ permeability between epithelial cells was concomitantly observed in the jejunum of fasted mice. Transepithelial glucose flux was assessed using a non-metabolizable glucose analog, 14C-methyl α-d-glucopyranoside glucose (MGP). Regardless of whether fed or fasted, no glucose diffusion mechanism was observed. Fasting increased the SGLT1-mediated MGP flux in the jejunum. In conclusion, segment-dependent up- and down-regulation mechanisms during fasting and feeding are important for efficient glucose absorption once the fast is broken. Additionally, these mechanisms may play a crucial role in the small intestine's ability to autoregulate glucose absorption, preventing acute hyperglycemia when large amounts of glucose are ingested.

Plant biomass as a source of low-temperature yeasts

More than 40 yeast strains were isolated from various types of plant biomass and then evaluated for potential applications in biotechnological processes conducted at low temperature. Adaptation to low temperature was tested by passaging the isolates at decreasing temperatures, from 30 to 15 °C. Only the strains that were able to adapt to the final temperature and reached the stationary growth phase relatively quickly were submitted to further experimentation. These included eight environmental yeast isolates from four types of materials of plant origin: wheat, rye, and cucumber, containing glucose, fructose, sucrose, and starch; yeast-fermentable sugars; red beetroot, containing large amounts of glucose and fructose; and fruits (grapes and apples) containing glucose, fructose, and sucrose. The strains were identified and then subjected to a series of experiments to assess their suitability for use in low-temperature biotechnological industrial processes incorporating microbial biomass. The growth dynamics and assimilation profiles of the yeast strains were investigated, as well as their ability to produce volatile compounds.

LBODP036 A Case of Euglycemic Diabetic Ketoacidosis After Distal Pancreatectomy

Abstract The patient is a 68-year-old female with a past medical history of type 2 diabetes mellitus, pancreatic mass, hypertension, hyperlipidemia, and coronary artery disease who presented to the hospital for elective surgical resection of her pancreatic mass. She underwent robotic-assisted laparoscopic distal pancreatectomy, splenectomy, and gastric wedge resection. Her hospital course was complicated by post-operative bleeding with hemoperitoneum the day after her initial surgery. She returned to the operative room for exploratory laparotomy during which the source of bleeding was identified and repaired. She was transferred to the intensive-care unit for post-operative monitoring. On the fourth day of admission, the patient became markedly acidotic. Her labs revealed a bicarbonate level of 12 mmol/L and a pH of 7.24. Her anion gap was elevated to 17. Endocrinology was consulted for suspected euglycemic diabetic ketoacidosis. Beta-hydroxybutyrate was elevated to 5.10 mmol/L (0 - 0.29 mmol/L). The patient's blood glucose was 159 mg/dL. Of note, the patient does take Empagliflozin at home. This medication has been associated with euglycemic diabetic ketoacidosis; however, she had not received this medication for five days prior to the onset of diabetic ketoacidosis. Glucosuria is expected to return to baseline after discontinuation of Empagliflozin within approximately three days. A urinalysis was checked at the time of consultation, and the patient did have a large amount of glucose in her urine which suggests that Empagliflozin was still acting to produce glucosuria. The patient was treated with intravenous insulin and fluids per the institution's protocol for the management of diabetic ketoacidosis. Her acidosis rapidly improved, and she was transitioned to subcutaneous insulin to manage her diabetes prior to discharge. This is an interesting case of euglycemic diabetic ketoacidosis due to the multifactorial precipitants: the dwindling effect of Empagliflozin five days after discontinuation, the loss pancreatic beta cell mass after distal pancreatectomy, and the stress of multiple surgeries complicated by life-threatening post-operative bleeding. Presentation: No date and time listed

Determination of Glucan Chain Length Distribution of Glycogen Using the Fluorophore-Assisted Carbohydrate Electrophoresis (FACE) Method

Glycogen particles are branched polysaccharides composed of linear chains of glucosyl units linked by α-1,4 glucoside bonds. The latter are attached to each other by α-1,6 glucoside linkages, referred to as branch points. Among the different forms of carbon storage (i.e., starch, β-glucan), glycogen is probably one of the oldest and most successful storage polysaccharides found across the living world. Glucan chains are organized so that a large amount of glucose can quickly be stored or fueled in a cell when needed. Numerous complementary techniques have been developed over the last decades to solve the fine structure of glycogen particles. This article describes Fluorophore-Assisted Carbohydrate Electrophoresis (FACE). This method quantifies the population of glucan chains that compose a glycogen particle. Also known as chain length distribution (CLD), this parameter mirrors the particle size and the percentage of branching. It is also an essential requirement for the mathematical modeling of glycogen biosynthesis.

Determination of Glucan Chain Length Distribution of Glycogen Using the Fluorophore-Assisted Carbohydrate Electrophoresis (FACE) Method.

Glycogen particles are branched polysaccharides composed of linear chains of glucosyl units linked by α-1,4 glucoside bonds. The latter are attached to each other by α-1,6 glucoside linkages, referred to as branch points. Among the different forms of carbon storage (i.e., starch, β-glucan), glycogen is probably one of the oldest and most successful storage polysaccharides found across the living world. Glucan chains are organized so that a large amount of glucose can quickly be stored or fueled in a cell when needed. Numerous complementary techniques have been developed over the last decades to solve the fine structure of glycogen particles. This article describes Fluorophore-Assisted Carbohydrate Electrophoresis (FACE). This method quantifies the population of glucan chains that compose a glycogen particle. Also known as chain length distribution (CLD), this parameter mirrors the particle size and the percentage of branching. It is also an essential requirement for the mathematical modeling of glycogen biosynthesis.

Insulin sensitivity and kinetics in African American and White people with obesity: Insights from different study protocols.

Studies that used an intravenous glucose tolerance test (IVGTT) have suggested that race is an important modulator of insulin sensitivity, β-cell function, and insulin clearance. However, the validity of the IVGTT has been challenged. This study assessed insulin sensitivity and insulin kinetics in non-Hispanic White (NHW, n = 29) and African American (AA, n = 14) people with obesity by using a hyperinsulinemic-euglycemic pancreatic clamp with glucose tracer infusion, an oral glucose tolerance test (OGTT), and an IVGTT. Hepatic insulin sensitivity was better in AA participants than in NHW participants. Muscle insulin sensitivity, insulin secretion in relation to plasma glucose during the OGTT, and insulin clearance during basal conditions during the hyperinsulinemic-euglycemic pancreatic clamp and during the OGTT were not different between AA participants and NHW participants. The acute insulin response to the large glucose bolus administered during the IVGTT was double in AA participants compared with NHW participants because of increased insulin secretion and reduced insulin clearance. AA individuals are not more insulin resistant than NHW individuals, and the β-cell response to glucose ingestion and postprandial insulin clearance are not different between AA individuals and NHW individuals. However, AA individuals have greater insulin secretory capacity and reduced insulin clearance capacity than NHW individuals and might be susceptible to hyperinsulinemia after consuming very large amounts of glucose.

Visualizing the effects of lactate dehydrogenase (LDH) inhibition and LDH-A genetic ablation in breast and lung cancer with hyperpolarized pyruvate NMR.

In many tumors, cancer cells take up large quantities of glucose and metabolize it into lactate, even in the presence of sufficient oxygen to support oxidative metabolism. It has been hypothesized that this malignant metabolic phenotype supports cancer growth and metastasis, and that reversal of this so-called "Warburg effect" may selectively harm cancer cells. Conversion of glucose to lactate can be reduced by ablation or inhibition of lactate dehydrogenase (LDH), the enzyme responsible for conversion of pyruvate to lactate at the endpoint of glycolysis. Recently developed inhibitors of LDH provide new opportunities to investigate the role of this metabolic pathway in cancer. Here we show that magnetic resonance spectroscopic imaging of hyperpolarized pyruvate and its metabolites in models of breast and lung cancer reveal that inhibition of LDH was readily visualized through reduction in label exchange between pyruvate and lactate, while genetic ablation of the LDH-A isoform alone had smaller effects. During the acute phase of LDH inhibition in breast cancer, no discernible bicarbonate signal was observed and small signals from alanine were unchanged.

In vitro and in vivo investigations of novel 1,4-napthoquinone sulphomethylene carbohydrate conjugates in prostate cancer.

104 Background: The Warburg effect describes the ability of cancer cells to consume larger amounts of glucose in comparison to normal tissue, due to the overexpression of insulin-independent glucose transporters (e.g. GLUT1). This effect can be used to enhance the selectivity and reduce side effects of cytotoxic anticancer molecules by its conjugation to sugar residues, thus, generating cytotoxic agents showing higher selectivity to cancer cells. In continuation of our research on anticancer natural 1,4-naphthoquinones we have investigated a large series of novel semi-synthetic molecules containing 1,4-naphthoquinones element conjugated with glucose molecule via -S-CH2- bond. Methods: We performed screening examinations for 35 novel synthetic molecules in human prostate cancer in vitro. The selected most active compounds were tested in several human prostate cancer cell lines harboring different levels of drug resistance, as well as in non-malignant cells to specify their selectivity. Compounds with the highest cytotoxicity and selectivity were further investigated. The mode of action was assessed including effects on apoptosis induction, oxidative stress, mitochondria, AR-signaling as well as glucose uptake and ER stress were assessed. In vivo dose finding and efficacy analyses were performed. Results: We identified two promising derivatives, showing IC50s at low micro- and nanomolar concentrations. Glucose depletion from the culture media led to increased cytotoxicity and cotreatment with a GLUT1-inhibitor showed an antagonistic effect, suggesting a concurrent uptake and therefore a Warburg effect targeting. The selected compounds exhibited most pronounced cytotoxic activity in DU145 cells as well as 22Rv1 cells. Non-malignant cells were generally less affected. The mode of action involves a loss of mitochondrial membrane potential, a release of cytochrome c and AIF into the cytosol and an upregulation of caspase-9, caspase-3 and cleaved PARP, as well as downregulation of Bcl-2 and Survivin, indicating that mitochondria are a major target, leading to the activation of the intrinsic apoptotic pathway. Early events in treated cells are ROS production and calcium release into the cytosol, a marker of ER-stress. Furthermore, downregulation of the AR and its signaling was observed on mRNA- and protein-level. In vivo experiments revealed antitumor activity in a 22Rv1-xenograft mouse model without severe side effects. Conclusions: In conclusion, we were able to identify two glucose-conjugated 1,4-naphthoquinones exhibiting potent in vitro and in vivoactivity and selectivity in human prostate cancer cells due to the Warburg effect targeting. Cytotoxic activity was exerted via initial ROS production and ER stress leading to mitochondrial damage and the induction of the intrinsic apoptotic pathway.

A regulatory switch in obesity

Metabolism The liver not only produces glucose but also consumes a large amount of glucose, making this organ critical for glucose homeostasis. Kokaji et al. performed multiomics analyses on the liver and blood of normal mice and in a genetic mouse model for obesity ( ob/ob ). Whereas normal hepatic metabolic responses to glucose were rapid and relied on regulation by metabolites, those in ob/ob mice were slow and depended on changes in gene expression. Thus, obesity in this model not only slows hepatic metabolic responses to glucose but also makes these responses more energy consuming and less precise. Sci. Signal. 13 , eaaz1236 (2020).

Lysosomal Lipoprotein Processing in Endothelial Cells Stimulates Adipose Tissue Browning

In response to thermogenic activation, brown adipose tissue (BAT) and white adipose tissue (WAT) internalize large amounts of glucose and lipids for energy combustion in brown and brite/beige adipocytes. It is well established that fatty acids are internalized by adipocytes after lipoprotein lipase-mediated hydrolysis of triglyceride-rich lipoproteins (TRL). Here, we show that in cold-exposed mice, vascular endothelial cells in thermogenic adipose tissues endocytose substantial amounts of entire TRL particles. These lipoproteins subsequently follow the endosomal/lysosomal pathway, where they undergo lysosomal acid lipase (LAL)-mediated processing. Endothelial cell-specific LAL-deficiency results in impaired thermogenic capacity that can be explained by reduced WAT browning. Mechanistically, TRL processing by LAL induces proliferation of endothelial cells and adipocyte precursors via a hypoxia-inducible factor-1a-dependent process. In conclusion, this study demonstrates a physiological role for TRL particle uptake into BAT and WAT, and establishes endothelial lipoprotein processing as an important determinant of adipose tissue remodeling during thermogenic adaptation.

1042-P: Insulin Requirement during Total Parenteral Nutrition in Patients with Diabetes Mellitus

Glycemic control in patients with diabetes mellitus receiving total parenteral nutrition (TPN) can be challenging due to multiple factors. These patients often have a high burden of illness and receive medications that raise blood glucose (BG) levels. Moreover, TPN delivers a large amount of glucose directly into the systemic circulation without the benefit of incretin effect. Therefore, relatively large amounts of insulin are expected to be required for glycemic control. However, there are no studies to guide insulin dosing in patients with diabetes being started on TPN. We conducted a retrospective study including all patients with diabetes admitted to our hospital over a 1-year period who received TPN for ≥ 3 days. The goal of this study was to estimate a safe starting dose of insulin for TPN. Patients receiving enteral nutrition along with TPN were excluded. Insulin doses and blood glucose levels on the last day of TPN were used for data analysis. We found 25 patients who fulfilled our inclusion/exclusion criteria. All patients had type 2 diabetes and were receiving antidiabetic drugs before hospitalization. Mean age was 68 ± 7 years, 56% were men, 80% were White, 44% had microvascular and 44% had macrovascular complications. Mean BMI was 26.7 ± 6.7 kg/m2, systolic BP 131 ± 27 mmHg, diastolic BP 65 ± 15 mmHg, HbA1c 7.7 ± 2.3% and serum creatinine 2.7 ± 3.3 mg/dl. The mean daily BG on TPN was 212 ± 47 mg/dl. Out of 171 BG values available on the last day of TPN, 116 (68%) were >180 mg/dl, 4 (2%) were <70 mg/dl and 0 were <40 mg/dl. Only two patients suffered mild hypoglycemic episodes while all others remained hyperglycemic. Average total daily insulin dose was 17 ± 20 units before starting TPN and 53 ± 54 units on the last day of TPN. Patients received an average of 0.7 Units/kg total daily dose of insulin on the last day of TPN. With this dose, they had minimal risk of hypoglycemia but the glucose levels were often high. Our study shows that the majority of patients with diabetes need more than 0.7 units/kg insulin when receiving TPN. Disclosure R. Garg: None. A. Arunachalam: None. L.E. Bermudez: None. M. Ramirez: None.

Metal ferrite incorporated polysulfone thin-film nanocomposite membranes for wastewater treatment.

Effluents from food, fermentation, and sugar industries contain a large quantity of glucose which has to be removed to limit the chemical oxygen demand (COD) of the water discharged. This work proposes novel thin-film nanocomposite (TFN) membranes incorporated with MgFe2O4 and ZnFe2O4 nanoparticles to address this concern. The nanoparticles synthesized by the sol-gel method was extensively characterized and then incorporated into the active polyamide layer of the thin-film composite polysulfone membranes. The change in membrane morphology, wettability, chemical structure, and mechanical strength with the incorporation of nanoparticles was studied in detail. Membranes with 0.005wt.% MgFe2O4 nanoparticle exhibited highest glucose rejection (96.52 ± 2.35%) at 10bar, 25°C, and sufficiently high pure water flux (50.54 ± 1.92L/m2h). This membrane also displayed 69.1 ± 5.12% salt rejection when challenged with 2000ppm synthetic NaCl solution.

POST SURGICAL BYPASS OF DIABETIC KETOACIDOSIS PROTOCOL

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Serum–glucose cotransporter-2 (SGLT-2) inhibitors are associated with potential euglycemic diabetic ketoacidosis (eDKA) in patients with type 1 and type 2 diabetes mellitus (T2DM). We describe a case of eDKA in a T2DM patient after gastric bypass surgery, treated with empagliflozin monotherapy, which exposed limitations of standardized DKA protocols. CASE PRESENTATION: A 49-year-old male with a history of morbid obesity and T2DM presented with three weeks of lethargy and weakness, in the setting of recent Roux-en-Y gastric bypass surgery. Previously, his T2DM was controlled with dulaglutide, insulin, and metformin. Following his surgery he was switched to empagliflozin only. On admission, the patient had a pH of 7.14, anion gap of 27, betahydroxybutyrate level of 9.98, ketonuria, and a glucose level of 178. In the ICU, he was maintained on IV insulin and D5/NS infusion. He required up to 8ml/hour of IV insulin due to difficulty controlling his ketoacidosis and consequently required high doses of supplemental dextrose, deviating substantially from standard DKA protocol. After 48 hours, his anion gap closed and he was transitioned to a subcutaneous basal-bolus insulin regimen. At discharge, empagliflozin was discontinued and he was prescribed a basal-bolus insulin regimen. DISCUSSION: SGLT-2 inhibitors present an invaluable option in managing diabetes mellitus. While SGLT-2 inhibitors are often used as monotherapy, eDKA can be clinically difficult to differentiate from routine complications of post-gastric bypass surgery. This may delay the diagnosis while increasing the severity of eDKA, health care costs, and length of hospital admission. The proposed mechanism of eDKA and SGLT-2 inhibitors involves increased urinary ketone reabsorption and large amounts of glucose in the urine in the presence of an increased rate of gluconeogenesis and free fatty acid release (1-3). Precipitants include a reduction of co-regimented insulin, alcohol consumption, infection, prolonged exercise, and reduced carbohydrate intake (1). In the post-operative setting, the duration of eDKA in patients with T2DM treated with SGLT-2 inhibitors is poorly defined and often requires several days of intravenous insulin therapy (1). Stopping this medication 24 to 48 hours prior to surgery, due to its half-life of about 12 hours, has not demonstrated significant benefit (1). CONCLUSIONS: SGLT-2 inhibitors present an invaluable option in managing diabetes mellitus. Importance of their risk to cause eDKA has become more relevant to prescribers, considering the increased number of case reports present to date. While SGLT-2 inhibitors are often used as monotherapy, eDKA can be clinically difficult to differentiate from routine complications of post-gastric bypass surgery. This may delay the diagnosis while increasing the severity of eDKA, health care costs, and length of hospital admission. Reference #1: Peters A., Buschur E., Buse J., Cohan P., Diner J., and Hirsch I. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care 2015 Sep; 38(9): 1687-1693 Reference #2: Bashir J., Nalla P., Peter R., Bain S., Chudleigh R. A Case Series of DKA Occuring in Patients Receiving Treatment with SGLT-2 Inbitors. Diabetes Obes Metab. 2018; 20:1800-1801 Reference #3: Ireland JT, Thomson WS. Euglycemic diabetic ketoacidosis. BMJ1973;3:107 DISCLOSURES: No relevant relationships by Rahul Chaudhari, source=Web Response No relevant relationships by Stephen Schwartz, source=Web Response No relevant relationships by cyrus vahdatpour, source=Web Response

Abstract 4372: Effects of high glucose and DCA on ROS production and viability of breast cancer cells with disrupted antioxidant systems

Abstract A goal of this study was to determine if disruption of protective cellular antioxidant systems would sensitize cancer cells to dichloroacetate (DCA), a compound affecting mitochondrial metabolism (reversing the Warburg Effect). DCA shifts the metabolism of glucose back to mitochondrial oxidative phosphorylation, with subsequent production of reactive oxygen species (ROS) (Bonnet et al., 2007). While cancer cells consume large amounts of glucose to meet energy demands and provide substrates necessary for protein and nucleic acid biosynthesis, they utilize aerobic glycolytic pathways (Warburg metabolism) instead of oxidative phosphorylation. Glutathione (GSH) and thioredoxin (Trx) are among the antioxidants produced to protect cells from oxidative damage; oxidative stress occurs when the production of ROS overwhelms these systems. Biosynthesis of GSH and Trx were inhibited by treating cells with low levels of buthionine sulfoximine (BSO) and auranofin (AUR) to deplete GSH and Trx, respectively. Through its stimulation of ROS production, DCA should enhance the cytotoxic effects in cells with diminished antioxidant systems. A second goal was to investigate the effects of these compounds on cells grown in either low or high glucose media (1 g/L vs 4.5 g/L). Cells grown under high glucose conditions were expected to produce more ROS and exhibit greater sensitivity to the combination of DCA, BSO and AUR. The experiments were conducted using MDA-MB-231 and MCF-7, breast cancer cell lines with known differences in metabolism and responses to chemotherapeutic drugs. BSO led to a dramatic decrease of GSH levels. AUR, at concentrations above 0.5 µM, significantly reduced cell viability when in combination with BSO. DCA alone reduced viability, but its effects were significantly enhanced when used in conjunction with BSO/AUR. Levels of ROS were quantified using a luminescence-based assay. In low glucose media, BSO/AUR and DCA had no effect on ROS production. In contrast, a high glucose environment led to elevated ROS production under all conditions, with the highest levels being induced by DCA in the cells having disrupted antioxidant systems. In the presence of BSO/AUR, MDA-MB-231 cells produced more ROS than MCF-7 cells. Overall, inhibition of antioxidant systems sensitized cells to DCA, increasing ROS and reducing viability.Previous studies have reported metabolic differences between cell lines (Gatenby and Gillies, 2004). MDA-MB-231 cells rely on aerobic glycolysis while MCF-7 cells are more reliant on mitochondrial oxidative phosphorylation. Therefore, MCF-7 cells have developed increased protection against ROS as compared to MDA-MB-231 cells (Theodossiou et al., 2017). These findings support the observed differences in response to BSO/AUR between the two cell lines. Paradoxically, MCF-7 cells were more sensitive to BSO/AUR than MDA-MB-231 cells in colony formation assays. Citation Format: Radek Buss, Collin Ellenbecker, Emily Minton, Lauren Gray, Mona Nolte, Aysiah Jaeke, Russ Feirer. Effects of high glucose and DCA on ROS production and viability of breast cancer cells with disrupted antioxidant systems [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4372.

Abstract SY24-02: Improving radio-sensitivity in cervical cancer by targeting tumor metabolism

Abstract Our group has previously shown that cervical cancers that take up large quantities of glucose, as defined by pretreatment 18F-fluoro-deoxy-glucose positron emission tomography (FDG-PET) imaging, are resistant to standard-of-care treatment (cisplatin plus concurrent pelvic irradiation). In this session, we will review the clinical evidence that supports this finding, and translational studies that support a connection between aberrant PI3K/AKT signaling and increased glucose uptake in tumors. We will then detail recent preclinical evidence that supports simultaneous inhibition of glycolysis and redox metabolism as an effective and safe alternative treatment strategy for highly glycolytic, radiation-resistant cervical cancers. Ongoing efforts to identify, characterize, and validate biomarkers to guide this strategy will be discussed. Citation Format: Julie K. Schwarz. Improving radio-sensitivity in cervical cancer by targeting tumor metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr SY24-02.

Sodium-glucose Cotransporter 2 Inhibitors: The Pleiotropic Mechanisms of Actions.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a new class of oral antidiabetic drugs. So far, there are three agents approved for use in Europe and in the USA, two in Japan and another four agents under testing. The purpose of this study is to describe the mechanism of action and the favorable and adverse effects of SGLT-2 inhibitors. A thorough review of literature indexed in PubMed, Scopus and Cochrane databases were conducted. Original papers, review papers and their relevant references in English, from 2005 to February 2017, were included. The main mechanism of action is the glycosuria induced by the inhibition of SGLT-2, located in the early segment of the proximal convoluted tubule. Along with large amounts of glucose, sodium, water and uric acid are also excessively excreted in urine. These actions have various, both desired and adverse, consequent implications in kidneys, blood pressure, cardiovascular system and other systems. Moreover, SGLT-2 inhibitors act directly to organs other than the kidneys, as SGLT-2 can be expressed there. The underlying mechanisms responsible for the SGLT-2 inhibitor actions, are pleiotropic and occur in the kidneys, as well as in other target organs. The comprehension of these mechanisms, not only permits us to understand their actions better, but it could also help us to predict more of their undisclosed favorable actions, as well as their rare adverse effects.

Nutritive Value of Desert Truffles Species of Genera Terfezia and Picoa (Ascomycetes) from Arid and Semiarid Regions of Eastern Turkey.

Terfezia and Picoa species contained 63-94 kcal energy, 76.93-83.81 g moisture, 0.78-1.52 g ash, 2.19-4.69 g protein, 2.14-9.48 g carbohydrate, 2.54-11.23 g dietary fiber, and 0.96-3.40 g fat per 100 g wet weight. We determined that Terfezia species contain more vitamin E and malondialdehyde than do Picoa species, but the amounts of vitamin A, vitamin C, and β-carotene may vary. Picoa species contain less palmitic and stearic acids but more oleic acid than do Terfezia species. Amino acid analyses revealed that glutamic and aspartic acid were the most abundant. We also noted that Picoa species have larger amounts of glucose and fructose than do Terfezia species. In addition, the elements these mushrooms contain can vary, but they are found at nutritious levels and are below toxic levels.

Restricting glycolysis impairs brown adipocyte glucose and oxygen consumption.

During thermogenic activation, brown adipocytes take up large amounts of glucose. In addition, cold stimulation leads to an upregulation of glycolytic enzymes. Here we have investigated the importance of glycolysis for brown adipocyte glucose consumption and thermogenesis. Using siRNA-mediated knockdown in mature adipocytes, we explored the effect of glucose transporters and glycolytic enzymes on brown adipocyte functions such as consumption of glucose and oxygen. Basal oxygen consumption in brown adipocytes was equally dependent on glucose and fatty acid oxidation, whereas isoproterenol (ISO)-stimulated respiration was fueled mainly by fatty acids, with a significant contribution from glucose oxidation. Knockdown of glucose transporters in brown adipocytes not only impaired ISO-stimulated glycolytic flux but also oxygen consumption. Diminishing glycolytic flux by knockdown of the first and final enzyme of glycolysis, i.e., hexokinase 2 (HK2) and pyruvate kinase M (PKM), respectively, decreased glucose uptake and ISO-stimulated oxygen consumption. HK2 knockdown had a more severe effect, which, in contrast to PKM knockdown, could not be rescued by supplementation with pyruvate. Hence, brown adipocytes rely on glucose consumption and glycolytic flux to achieve maximum thermogenic output, with glycolysis likely supporting thermogenesis not only by pyruvate formation but also by supplying intermediates for efferent metabolic pathways.