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https://www.readbyqxmd.com/read/28098449/targeting-type-2-diabetes-with-c-glucosyl-dihydrochalcones-as-selective-sodium-glucose-co-transporter-2-sglt2-inhibitors-synthesis-and-biological-evaluation
#1
Ana R Jesus, Diogo Vila-Viçosa, Miguel Machuqueiro, Ana P Marques, Timothy M Dore, Amélia P Rauter
Inhibiting glucose reabsorption by sodium glucose co-transporter proteins (SGLTs) in the kidneys is a relatively new strategy for treating type 2 diabetes. Selective inhibition of SGLT2 over SGLT1 is critical for minimizing adverse side effects associated with SGLT1 inhibition. A library of C-glucosyl dihydrochalcones and their dihydrochalcone and chalcone precursors was synthesized and tested as SGLT1/SGLT2 inhibitors using a cell-based fluorescence assay of glucose uptake. The most potent inhibitors of SGLT2 (IC50 = 9-23 nM) were considerably weaker inhibitors of SGLT1 (IC50 = 10-19 μM)...
January 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28098405/shielding-engineered-islets-with-mesenchymal-stem-cells-enhance-survival-under-hypoxia
#2
Bhawna Chandravanshi, Ramesh Ramchandra Bhonde
In the present study we focused on the improvisation of islet survival in hypoxia.The Islet like cell aggregates (ICAs) derived from wharton's jelly mesenchymal stem cells (WJ MSC) were cultured with and without WJ MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin,Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitated highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay...
January 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28096436/angiotensin-ii-induces-differential-insulin-action-in-rat-skeletal-muscle
#3
Juthamard Surapongchai, Mujalin Prasannarong, Tepmanas Bupha-Intr, Vitoon Saengsirisuwan
Angiotensin II (ANGII) is reportedly involved in the development of skeletal muscle insulin resistance. The present investigation evaluated the effects of two ANGII doses on the phenotypic characteristics of insulin resistance syndrome and insulin action and signaling in rat skeletal muscle. Male Sprague-Dawley rats were infused with either saline (SHAM) or ANGII at a commonly used pressor dose (100 ng/kg/min; ANGII-100) or a higher pressor dose (500 ng/kg/min; ANGII-500) via osmotic minipumps for 14 days. We demonstrated that ANGII-100-infused rats exhibited the phenotypic features of non-obese insulin resistance syndrome, including hypertension, impaired glucose tolerance and insulin resistance of glucose uptake in the soleus muscle, whereas ANGII-500-treated rats exhibited diabetes-like symptoms, such as post-prandial hyperglycemia, impaired insulin secretion and hypertriglyceridemia...
January 17, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28095750/effects-of-pre-germinated-brown-rice-treatment-high-fat-diet-induced-metabolic-syndrome-in-c57bl-6j-mice
#4
Hsueh-Wei Yen, Hui-Li Lin, Chi-Long Hao, Fu-Chih Chen, Chun-Yun Chen, Jia-Hao Chen, Kuo-Ping Shen
To investigate using pre-germinated brown rice (PGBR) to treat metabolic syndrome, we fed one group of mice standard-regular-diet (SRD) for 20 weeks and another group of mice high-fat-diet (HFD) for 16 weeks. We subdivided them into HFD group and HFD + PGBR group whose dietary carbohydrate was replaced with PGBR for 4 weeks. The HFD group gained more weight, had higher blood pressure, heart rate, blood glucose and lipids, liver levels of TG, feces TG and bile acid, lower adipose levels of adipocytokine, lower skeletal muscle IR, IRS-1, IRS-2, PI3 K, Akt/PKB, GLUT-1, GLUT-4, GCK and PPAR-γ; higher liver SREBP-1, SCD-1, FAS, HMGCR, LDLR, CYP7α1 and PPAR-α, and higher adipose SREBP-1, SCD-1, FAS, and lower adipose PPAR-α and adiponectin...
January 18, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28093310/effects-of-glucose-and-insulin-administration-on-glucose-transporter-expression-in-the-north-pacific-spiny-dogfish-squalus-suckleyi
#5
Courtney A Deck, W Gary Anderson, Patrick J Walsh
Elasmobranchs (sharks, skates, and rays) are a primarily carnivorous group of fish, consuming few carbohydrates. Further, they tend to exhibit delayed responses to glucose and insulin administration in vivo relative to mammals, leading to a presumption of glucose-intolerance. To investigate the glucoregulatory capabilities of the spiny dogfish (Squalus suckleyi), plasma glucose concentration, muscle and liver glycogen content, and glucose transporter (glut1 and 4) mRNA levels were measured following intra-arterial administration of bovine insulin (10 ng kg(-1)) or an approximate doubling of fasting plasma glucose concentration...
January 13, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28073046/olanzapine-and-aripiprazole-differentially-affect-glucose-uptake-and-energy-metabolism-in-human-mononuclear-blood-cells
#6
Britta Stapel, Alexandra Kotsiari, Michaela Scherr, Denise Hilfiker-Kleiner, Stefan Bleich, Helge Frieling, Kai G Kahl
The use of antipsychotics carries the risk of metabolic side effects, such as weight gain and new onset type-2 diabetes mellitus. The mechanisms of the observed metabolic alterations are not fully understood. We compared the effects of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (aripiprazole), on glucose metabolism. Primary human peripheral blood mononuclear cells (PBMC) were isolated and stimulated with olanzapine or aripiprazole for 72 h. Cellular glucose uptake was analyzed in vitro by 18F-FDG uptake...
December 22, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28068944/the-acceleration-of-glucose-accumulation-in-renal-cell-carcinoma-assessed-by-fdg-pet-ct-demonstrated-acquisition-of-resistance-to-tyrosine-kinase-inhibitor-therapy
#7
Noboru Nakaigawa, Keiichi Kondo, Daiki Ueno, Kazuhiro Namura, Kazuhide Makiyama, Kazuki Kobayashi, Koichi Shioi, Ichiro Ikeda, Takeshi Kishida, Tomohiro Kaneta, Ryogo Minamimoto, Ukihide Tateishi, Tomio Inoue, Masahiro Yao
BACKGROUND: Tyrosine-kinase inhibitor (TKI) targeting angiogenesis improves the prognosis of patients with metastatic renal cell carcinoma (RCC), but its effect is temporary. In order to understand the mechanism by which RCC acquires resistance to TKI, we investigated the change of glucose accumulation in RCC by FDG PET/CT when they demonstrated progression disease (PD) against TKI. METHODS: We monitored the FDG accumulation in RCC of 38 patients treated with TKI by 162 PET/CT sequentially until they were judged to demonstrate PD...
January 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28065232/establishment-of-an-alloxan-induced-diabetes-model-in-daphnia-pulex
#8
An-Min Hu, Tao Zhu, Ye Jiang, Li Dong, Hong Gao, Gui-Zhi DU
Objective To establish a Daphnia model of alloxan-induced diabetes. Methods Daphnia were exposed to three different concentrations of alloxan (3, 5, and 10 mmol/L) for 30 minutes. Blood glucose and survival rate were recorded for 72 hours after alloxan insult. Sequence analysis and phylogenetic inference for glucose transporters (GLUT) were clustered with the maximum-likelihood method. Using reverse transcription and quantitative polymerase chain reaction techniques, we investigated the transcriptional changes of GLUT at 12 hours after alloxan (5 mmol/L) exposure...
December 20, 2016: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/28063949/vitamin-d-supplementation-inhibits-oxidative-stress-and-upregulate-sirt1-ampk-glut4-cascade-in-high-glucose-treated-3t3l1-adipocytes-and-in-adipose-tissue-of-high-fat-diet-fed-diabetic-mice
#9
Prasenjit Manna, Arunkumar E Achari, Sushil K Jain
This study examined the hypothesis that vitamin-D prevents oxidative stress and upregulates glucose metabolism via activating insulin-independent signaling molecules in 3T3-L1 adipocytes and in high fat diet (HFD)-fed mice. To investigate the mechanism 3T3L1 adipocytes were treated with high glucose (HG, 25 mM) and 1,25(OH)2D3 (1,25-dihydroxyvitamin D3) (0-50 nM). Results showed that 1,25(OH)2D3 supplementation decreased NOX4 expression, ROS production, NF-κB phosphorylation, and increased the expression of Nrf2 and Trx in HG-treated cells...
January 4, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28061796/glucose-transporter-4-promotes-head-and-neck-squamous-cell-carcinoma-metastasis-through-the-trim24-ddx58-axis
#10
Yu-Chan Chang, Li-Hsing Chi, Wei-Ming Chang, Chia-Yi Su, Yuang-Feng Lin, Chi-Long Chen, Ming-Huang Chen, Peter Mu-Hsin Chang, Alex T H Wu, Michael Hsiao
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) represents a unique and major health concern worldwide. Significant increases in glucose uptake and aerobic glycolysis have been observed in HNSCC cells. Glucose transporters (GLUTs) represent a major hub in the glycolysis pathway, with GLUT4 having the highest glucose affinity. However, GLUT4's role in HNSCC has not been fully appreciated. METHODS: An in silico analysis was performed in HNSCC cohorts to identify the most significant glucose transporter associated with HNSCC patient prognosis...
January 7, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28061344/monitoring-of-persistent-organic-pollutants-in-the-polar-regions-knowledge-gaps-gluts-through-evidence-mapping
#11
Maria Cristina Mangano, Gianluca Sarà, Simonetta Corsolini
Persistent organic pollutants (POPs) are widespread compounds that accumulating in polar regions canalise through trophic webs. Although several dozens of studies have been carried out in the last decades, the information is generally scattered across a large number of literature sources. This does not allow an efficient synthesis and constraints our understanding on how address future monitoring plans and environmental conservation strategies on the Polar Regions with respect to POPs. Thus, here, we present the outcome of a systematic map (SM) to scope, screen and chart evidences from literature dealing with POPs in Polar regions...
December 28, 2016: Chemosphere
https://www.readbyqxmd.com/read/28059465/rosmarinic-acid-mediates-mitochondrial-biogenesis-in-insulin-resistant-skeletal-muscle-through-activation-of-ampk
#12
Govindaraj Jayanthy, Vellai Roshana Devi, Kaliappan Ilango, Sorimuthu Pillai Subramanian
Rosmarinic acid (RA), a polyphenol, is known to improve hepatic insulin sensitivity in experimental type 2 diabetes. However, its effect on skeletal muscle insulin resistance is meagerly understood. The present study was aimed to investigate the upstream and downstream mediators of the molecular targets of RA in attenuating insulin resistance in the skeletal muscle both in vivo and in vitro. We found that supplementation of RA increased the expression of key genes involved in the mitochondrial biogenesis like PGC-1α, SIRT-1 and TFAM via activation of AMPK in the skeletal muscle of insulin resistant rats as well as in L6 myotubes...
January 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28053105/epstein-barr-virus-encoded-latent-membrane-protein-1-upregulates-glucose-transporter-1-transcription-via-the-mtorc1-nf-%C3%AE%C2%BAb-signaling-pathways
#13
Jun Zhang, Lin Jia, Weitao Lin, Yim Ling Yip, Kwok Wai Lo, Victoria Ming Yi Lau, Dandan Zhu, Chi Man Tsang, Yuan Zhou, Wen Deng, Hong Lok Lung, Maria Li Lung, Lai Man Cheung, Sai Wah Tsao
: Accumulating evidence indicates that oncogenic viral protein exerts a crucial role in activating aerobic glycolysis during tumorigenesis, but the underlying mechanisms are largely undefined. The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a trans-membrane protein with potent cell signaling properties and has tumorigenic transformation property. Activation of NF-κB is a major signaling pathway mediating many downstream transformation properties of LMP1. Here we report that activation of mTORC1 by LMP1 is a key modulator for activation of NF-κB signaling to mediate aerobic glycolysis...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28052033/glut-1-overexpression-as-an-unfavorable-prognostic-biomarker-in-patients-with-colorectal-cancer
#14
Jing Yang, Jing Wen, Tian Tian, Zhongsheng Lu, Yao Wang, Zikai Wang, Xiangdong Wang, Yunsheng Yang
BACKGROUND: Glucose transporter-1 (GLUT-1) exhibits altered expression in colorectal cancer (CRC). The aim of this study was to explore the association between GLUT-1 and survival conditions, as well as clinical features in CRC by meta-analysis. MATERIALS AND METHODS: Relevant studies were searched through predefined strategies, hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs) were used as effective measures. RESULTS: A total of 14 studies with 2,077 patients were included in this meta-analysis...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28042452/anticancer-agents-interacting-with-membrane-glucose-transporters
#15
C Granchi, S Fortunato, F Minutolo
The altered metabolism observed in cancer cells generally consists in increased glucose uptake and glycolytic activity. This is associated with an overexpression of glucose transporter proteins (GLUTs), which facilitate glucose uptake across the plasma membrane and play a crucial role in the survival of cancer cells. Therefore GLUTs are considered as suitable targets for the treatment of cancer. Herein we review some of the most relevant GLUT inhibitors that have been recently developed as prospective anticancer agents...
September 1, 2016: MedChemComm
https://www.readbyqxmd.com/read/28036029/fenofibrate-therapy-restores-antioxidant-protection-and-improves-myocardial-insulin-resistance-in-a-rat-model-of-metabolic-syndrome-and-myocardial-ischemia-the-role-of-angiotensin-ii
#16
Luz Ibarra-Lara, María Sánchez-Aguilar, Alicia Sánchez-Mendoza, Leonardo Del Valle-Mondragón, Elizabeth Soria-Castro, Elizabeth Carreón-Torres, Eulises Díaz-Díaz, Héctor Vázquez-Meza, Verónica Guarner-Lans, María Esther Rubio-Ruiz
Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia...
December 28, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28034722/specific-regions-of-the-brain-are-capable-of-fructose-metabolism
#17
Sarah A Oppelt, Wanming Zhang, Dean R Tolan
High fructose consumption in the Western diet correlates with disease states such as obesity and metabolic syndrome complications, including type II diabetes, chronic kidney disease, and non-alcoholic fatty acid liver disease. Liver and kidneys are responsible for metabolism of 40-60% of ingested fructose, while the physiological fate of the remaining fructose remains poorly understood. The primary metabolic pathway for fructose includes the fructose-transporting solute-like carrier transport proteins 2a (SLC2a or GLUT), including GLUT5 and GLUT9, ketohexokinase (KHK), and aldolase...
December 26, 2016: Brain Research
https://www.readbyqxmd.com/read/28034640/oral-perineurioma-clinicopathologic-features-from-two-cases-and-review-of-literature
#18
Wagner Gomes da Silva, Marisol Martínez Martínez, Águida Maria Menezes Aguiar Miranda, Roberto Bastos Silva, Henrique Martins da Silveira, Oslei Paes de Almeida, Fábio Ramôa Pires
The present study reports two cases of oral perineuriomas, including a clinicopathologic review of the 39 published cases (17 intraneural and 22 extraneural perineuriomas) in the English language literature. In the first case, the tumor occurred in an 84-year-old male as a painless, asymptomatic, 20-mm submucosal nodule on the right lower mucobuccal fold near to the premolar area. In the second case, a 46-year-old female presented with a painless, 25-mm, slow-growing, fibrous, pedunculated nodule on the right buccal mucosa...
October 12, 2016: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28034463/glucose-transporters-in-healthy-heart-and-in-cardiac-disease
#19
REVIEW
Leszek Szablewski
Heart consumes more energy than any other organ. It can utilize various metabolic substrates as a source of energy. The primary substrates are free fatty acids, especially long-chain fatty acids and glucose. The lipid bilayer of plasmalemma is impermeable for glucose. Therefore, glucose transport across the plasma membrane is mediated via glucose transporters. In human, cardiac cells are expressed as 2 families of glucose transporters: GLUTs and SGLTs. These transport proteins are GLUT1, GLUT3, GLUT8, GLUT10, GLUT11, GLUT12 and SGLT1...
December 21, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28028797/glut1-mct1-4-and-cd147-overexpression-supports-the-metabolic-reprogramming-in-papillary-renal-cell-carcinoma
#20
L M C A Almeida, R Silva, B Cavadas, J Lima, L Pereira, P Soares, M Sobrinho-Simões, J M Lopes, V Máximo
Papillary Renal Cell carcinoma (pRCC) is the second most common type of RCC, accounting for about 15% of all RCCs. Surgical excision is the main treatment option. Still, 10 - 15 % of clinically localized tumours will recur and/or develop metastasis early after surgery, and no reliable prognostic biomarkers are available to identify them. It is known that pRCC cells rely on high rates of aerobic glycolysis, characterized by the up-regulation of many proteins and enzymes related with the glycolytic pathway. However, a metabolic signature enabling the identification of advanced pRCC tumours remains to be discovered...
December 28, 2016: Histology and Histopathology
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