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https://www.readbyqxmd.com/read/28101792/medical-management-of-diabesity-do-we-have-realistic-targets
#1
REVIEW
Joseph M Pappachan, Ananth K Viswanath
PURPOSE OF REVIEW: The global prevalence of "diabesity"-diabetes related to obesity-is increasing steadily over the past few decades because of the obesity epidemic. Although bariatric surgery is an effective treatment option for patients with diabesity, its limited availability, invasiveness, relatively high costs and the potential for surgical and postsurgical complications restrict its widespread use. Therefore, medical management is the only option for a majority of patients with diabesity...
January 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28101749/twenty-seven-years-of-cerebral-pyruvate-recycling
#2
Sebastián Cerdán
Cerebral pyruvate recycling is a metabolic pathway deriving carbon skeletons and reducing equivalents from mitochondrial oxaloacetate and malate, to the synthesis of mitochondrial and cytosolic pyruvate, lactate and alanine. The pathway allows both, to provide the tricarboxylic acid cycle with pyruvate molecules produced from alternative substrates to glucose and, to generate reducing equivalents necessary for the operation of NADPH requiring processes. At the cellular level, pyruvate recycling involves the activity of malic enzyme, or the combined activities of phosphoenolpyruvate carboxykinase and pyruvate kinase, as well as of those transporters of the inner mitochondrial membrane exchanging the corresponding intermediates...
January 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28101358/novel-predictive-biomarkers-for-cervical-cancer-prognosis
#3
Pablo Moreno-Acosta, Schyrly Carrillo, Oscar Gamboa, Alfredo Romero-Rojas, Jinneth Acosta, Monica Molano, Joseph Balart-Serra, Martha Cotes, Chloé Rancoule, Nicolas Magné
High hypoxic, glycolytic and acidosis metabolisms characterize cervical cancer tumors and have been described to be involved in chemoradioresistance mechanisms. Based on these observations, the present study assessed four selected novel biomarkers on the prognosis of locally advanced cervical carcinoma. A total of 66 patients with stage IIB/IIIB cervical cancer were retrospectively included. The protein expression levels of glucose transporter 1 (GLUT1), carbonic anhydrase 9 (CAIX) and hexokinase 1 (HKII) were investigated by immunohistochemistry on tumor biopsies, hemoglobin was measured and the disease outcome was monitored...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28100752/differential-vulnerability-of-ca1-versus-ca3-pyramidal-neurons-after-ischemia-possible-relationship-to-sources-of-zn2-accumulation-and-its-entry-into-and-prolonged-effects-on-mitochondria
#4
Yuliya V Medvedeva, Sung G Ji, Hong Z Yin, John H Weiss
: Excitotoxic mechanisms contribute to the degeneration of hippocampal pyramidal neurons after recurrent seizures and brain ischemia. However, susceptibility differs, with CA1 neurons degenerating preferentially after global ischemia and CA3 neurons after limbic seizures. Whereas most studies address contributions of excitotoxic Ca(2+) entry, it is apparent that Zn(2+) also contributes, reflecting accumulation in neurons either after synaptic release and entry through postsynaptic channels or upon mobilization from intracellular Zn(2+)-binding proteins such as metallothionein-III (MT-III)...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
#5
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/28097490/glucose-uptake-and-triacylglycerol-synthesis-are-increased-in-barth-syndrome-lymphoblasts
#6
Edgard M Mejia, James C Zinko, Kristin D Hauff, Fred Y Xu, Amir Ravandi, Grant M Hatch
Barth syndrome (BTHS) is an X-linked genetic disease resulting in loss of cardiolipin (Ptd2Gro). Patients may be predisposed to hypoglycemia and exhibit increases in whole-body glucose disposal rates and a higher fat mass percentage. We examined the reasons for this in BTHS lymphoblasts. BTHS lymphoblasts exhibited a 60% increase (p < 0.004) in 2-[1,2-(3)H(N)]deoxy-D-glucose uptake, a 40% increase (p < 0.01) in glucose transporter-3 protein expression, an increase in phosphorylated-adenosine monophosphate kinase (AMPK) and a 58% increase (p < 0...
January 17, 2017: Lipids
https://www.readbyqxmd.com/read/28096442/kinetic-modeling-of-incremental-ambulatory-peritoneal-dialysis-exchanges
#7
Steven Guest, John K Leypoldt, Michelle E Cassin, Martin J Schreiber
♦ Background: Incremental peritoneal dialysis (PD), the gradual introduction of dialysate exchanges at less than full-dose therapy, has been infrequently described in clinical reports. One concern with less than full-dose dialysis is whether urea clearance targets are achievable with an incremental regimen. In this report, we used a large database of PD patients, across all membrane transport types, and performed urea kinetic modeling determinations of possible incremental regimens for an individual membrane type...
January 17, 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
https://www.readbyqxmd.com/read/28093310/effects-of-glucose-and-insulin-administration-on-glucose-transporter-expression-in-the-north-pacific-spiny-dogfish-squalus-suckleyi
#8
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/28093214/the-upr-reduces-glucose-metabolism-via-ire1-signaling
#9
Judith M van der Harg, Jessica C van Heest, Fabian N Bangel, Sanne Patiwael, Jan R T van Weering, Wiep Scheper
Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis...
January 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28092823/ph-lactate-and-hypoxia-reciprocity-in-regulating-high-affinity-monocarboxylate-transporter-expression-in-glioblastoma
#10
James P Caruso, Brandon J Koch, Philip D Benson, Elsa Varughese, Michael D Monterey, Amy E Lee, Ajal M Dave, Sam Kiousis, Andrew E Sloan, Saroj P Mathupala
Highly malignant brain tumors harbor the aberrant propensity for aerobic glycolysis, the excessive conversion of glucose to lactic acid even in the presence of ample tissue oxygen. Lactic acid is rapidly effluxed to the tumor microenvironment via a group of plasma-membrane transporters denoted monocarboxylate transporters (MCTs) to prevent "self-poisoning." One isoform, MCT2, has the highest affinity for lactate and thus should have the ability to respond to microenvironment conditions such as hypoxia, lactate, and pH to help maintain high glycolytic flux in the tumor...
January 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28092602/the-investigation-of-correlation-among-selected-biochemical-parameters-and-vital-signs-in-dairy-herd-to-design-the-bio-cybernetic-dairy-cow-model
#11
J Twardoń, W Zalewski, T Nowicki, B Dębski, G Dejneka, J Mrowiec, K Zalewski
The paper presents investigations of the relationship between the biochemical parameters and vital signs in dairy cows. We analyzed the welfare and functioning of a dairy herd using biochemical parameters and vital signs. Life and biochemical parameters were examined. In the model indicators useful for monitoring the herd are: the age of the cows, the number of cows' lactating, daily amount of received milk, length of lactation period for cows in the herd, the length of inter-calving period for cows, the number of days to effective insemination, the amount of protein in the feed, the level of β-oxidation in leucocytes, glucose transport through red blood cells and plasma insulin...
December 1, 2016: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/28092161/estimation-of-ellagic-acid-and-or-repaglinide-effects-on-insulin-signaling-oxidative-stress-and-inflammatory-mediators-of-liver-pancreas-adipose-tissue-and-brain-in-insulin-resistant-type-2-diabetic-rats
#12
Mohamed M Amin, Mahmoud S Arbid
Even though ellagic acid has previously been valued in many models of cancer, so far its full mechanistic effect as a natural antiapoptotic agent in the prevention of type 2 diabetes complications has not been completely elucidated, which was the goal of this study. We fed albino rats a high-fat fructose diet (HFFD) for 2 months to induce insulin resistance/type 2 diabetes and then treated the rats with ellagic acid (10 mg/kg body weight, orally) and/or repaglinide (0.5 mg/kg body weight, orally) for 2 weeks...
October 21, 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28090774/biakamides-a-d-unique-polyketides-from-a-marine-sponge-act-as-selective-growth-inhibitors-of-tumor-cells-adapted-to-nutrient-starvation
#13
Naoyuki Kotoku, Ryosuke Ishida, Hirokazu Matsumoto, Masayoshi Arai, Kazunari Toda, Andi Setiawan, Osamu Muraoka, Motomasa Kobayashi
Biakamides A-D, novel unusually unique polyketides, were isolated from an Indonesian marine sponge (Petrosaspongia sp.) with a constructed bioassay using PANC-1 human pancreatic cancer cells. Through detailed analyses of the one- and two-dimensional nuclear magnetic resonance (NMR) spectra of biakamides, planar chemical structures possessing a terminal thiazole, two N-methyl amides, a chloromethylene, and a substituted butyryl moiety were obtained. After elucidation of the configuration of the secondary alcohol moiety in biakamides A and B, the absolute stereostructures of the two secondary methyl groups in biakamides A-D were determined by the asymmetric total syntheses of all possible stereoisomers from the optically pure monoprotected 2,4-dimethyl-1,5-diol...
January 16, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28089907/adenosine-and-preeclampsia
#14
REVIEW
Rocío Salsoso, Marcelo Farías, Jaime Gutiérrez, Fabián Pardo, Delia I Chiarello, Fernando Toledo, Andrea Leiva, Alfonso Mate, Carmen M Vázquez, Luis Sobrevia
Adenosine is an endogenous nucleoside with pleiotropic effects in different physiological processes including circulation, renal blood flow, immune function, or glucose homeostasis. Changes in adenosine membrane transporters, adenosine receptors, and corresponding intracellular signalling network associate with development of pathologies of pregnancy, including preeclampsia. Preeclampsia is a cause of maternal and perinatal morbidity and mortality affecting 3-5% of pregnancies. Since the proposed mechanisms of preeclampsia development include adenosine-dependent biological effects, adenosine membrane transporters and receptors, and the associated signalling mechanisms might play a role in the pathophysiology of preeclampsia...
January 12, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28089828/nitrite-increases-glucose-stimulated-insulin-secretion-and-islet-insulin-content-in-obese-type-2-diabetic-male-rats
#15
Sevda Gheibi, Fatemeh Bakhtiarzadeh, Sajad Jeddi, Khadijeh Farrokhfall, Homeira Zardooz, Asghar Ghasemi
PURPOSE: Reduced bioavailability of nitric oxide (NO) is associated with pathogenesis of type 2 diabetes. Nitrite can act as a substrate for generation of systemic NO. The aim of this study was to examine the effects of nitrite administration on glucose-stimulated insulin secretion (GSIS) and islet insulin content in obese type 2 diabetic rats. METHODS: Male rats were divided into 4 groups: Control, control + nitrite, diabetes, and diabetes + nitrite. Sodium nitrite (50 mg/L in drinking water) was administered for 8 weeks...
January 9, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28089735/effects-of-simvastatin-on-cat-1-mediated-arginine-transport-and-no-level-under-high-glucose-conditions-in-conditionally-immortalized-rat-inner-blood-retinal-barrier-cell-lines-tr-ibrb
#16
Temdara Tun, Young-Sook Kang
OBJECTIVE: Hyperglycemia causes the breakdown of the blood-retinal barrier by impairing endothelial nitric oxide synthase (eNOS) function. Statins have many pleiotropic effects such as improving endothelial barrier permeability and increasing eNOS mRNA stability. The objective of this study was to determine effect of simvastatin on l-arginine transport and NO production under high-glucose conditions in conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB). METHODS: Changes in l-arginine transport uptake and, expression levels of cationic amino acid transporter 1 (CAT-1) and eNOS mRNA were investigated after pre-treatment with simvastatin and NOS inhibitors (l-NMMA and l-NAME) under high-glucose conditions using TR-iBRB, an in vitro model of iBRB...
January 12, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28089623/which-treatment-for-type-2-diabetes-associated-with-non-alcoholic-fatty-liver-disease
#17
REVIEW
Arianna Mazzotti, Maria Turchese Caletti, Francesca Marchignoli, Giulia Forlani, Giulio Marchesini
Type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD) are highly prevalent in the community, and share common pathogenic mechanisms. There is also evidence that T2DM may be favored by hepatic fat accumulation; in turn the presence of T2DM is a risk factor for liver disease progression. The treatment of T2DM has considerably changed in the past few years; new drug classes, promoting glucose-lowering through mechanisms different from classical insulin-sensitizing or insulin-secreting action, have been added to continuing lifestyle intervention...
December 30, 2016: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28086951/sodium-glucose-transporter-2-sglt2-inhibition-with-empagliflozin-improves-cardiac-diastolic-function-in-a-female-rodent-model-of-diabetes
#18
Javad Habibi, Annayya R Aroor, James R Sowers, Guanghong Jia, Melvin R Hayden, Mona Garro, Brady Barron, Eric Mayoux, R Scott Rector, Adam Whaley-Connell, Vincent G DeMarco
Obese and diabetic individuals are at increased risk for impairments in diastolic relaxation and heart failure with preserved ejection fraction. The impairments in diastolic relaxation are especially pronounced in obese and diabetic women and predict future cardiovascular disease (CVD) events in this population. Recent clinical data suggest sodium glucose transporter-2 (SGLT2) inhibition reduces CVD events in diabetic individuals, but the mechanisms of this CVD protection are unknown. To determine whether targeting SGLT2 improves diastolic relaxation, we utilized empagliflozin (EMPA) in female db/db mice...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28086872/dapagliflozin-decreases-small-dense-low-density-lipoprotein-cholesterol-and-increases-high-density-lipoprotein-2-cholesterol-in-patients-with-type-2-diabetes-comparison-with-sitagliptin
#19
Toshiyuki Hayashi, Tomoyasu Fukui, Noriko Nakanishi, Saki Yamamoto, Masako Tomoyasu, Anna Osamura, Makoto Ohara, Takeshi Yamamoto, Yasuki Ito, Tsutomu Hirano
BACKGROUND: The sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been reported to increase both low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol (C). This study aimed to determine how SGLT-2 inhibitors affect LDL and HDL-C subspecies. METHODS: This single center, open-label, randomized, prospective study included 80 patients with type 2 diabetes taking prescribed oral hypoglycemic agents. Patients were allocated to receive dapagliflozin (n = 40) or sitagliptin (n = 40) as add-on treatment...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28080219/adipose-tissue-insulin-resistance-in-gestational-diabetes
#20
Batbayar Tumurbaatar, Aaron T Poole, Gayle Olson, Michel Makhlouf, Hanaa S Sallam, Shwetha Thukuntla, Sucharitha Kankanala, Obos Ekhaese, Guillermo Gomez, Manisha Chandalia, Nicola Abate
BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance (IR) and altered glucose-lipid metabolism. We propose that ectonucleotide pyrophosphate phosphodiesterase-1 (ENPP1), a protein known to induce adipocyte IR, is a determinant of GDM. Our objective was to study ENPP1 expression in adipose tissue (AT) of obese pregnant women with or without GDM, as well as glucose tolerance in pregnant transgenic (Tg) mice with AT-specific overexpression of human ENPP1...
January 12, 2017: Metabolic Syndrome and related Disorders
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