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https://www.readbyqxmd.com/read/28346464/sympathetic-nervous-system-activity-and-anti-lipolytic-response-to-iv-glucose-load-in-subcutaneous-adipose-tissue-of-obese-and-obese-type-2-diabetic-subjects
#1
Uwe Schumann, Christopher P Jenkinson, Andreas Alt, Martina Zügel, Jürgen M Steinacker, Marion Flechtner-Mors
The study aim was to investigate the effect of endogenous insulin release on lipolysis in subcutaneous adipose tissue after adrenergic stimulation in obese subjects diagnosed with type 2 diabetes (T2D). In 14 obese female T2D subjects, or 14 obese non-T2D controls, glycerol concentration was measured in response to the α1,2,ß-agonist norepinephrine, the α1-agonist norfenefrine and the ß2-agonist terbutaline (each 10-4 M), using the microdialysis technique. After 60 minutes of stimulation, an intravenous glucose load (0...
2017: PloS One
https://www.readbyqxmd.com/read/28346406/diabetes-reversal-by-inhibition-of-the-low-molecular-weight-tyrosine-phosphatase
#2
Stephanie M Stanford, Alexander E Aleshin, Vida Zhang, Robert J Ardecky, Michael P Hedrick, Jiwen Zou, Santhi R Ganji, Matthew R Bliss, Fusayo Yamamoto, Andrey A Bobkov, Janna Kiselar, Yingge Liu, Gregory W Cadwell, Shilpi Khare, Jinghua Yu, Antonio Barquilla, Thomas D Y Chung, Tomas Mustelin, Simon Schenk, Laurie A Bankston, Robert C Liddington, Anthony B Pinkerton, Nunzio Bottini
Obesity-associated insulin resistance plays a central role in type 2 diabetes. As such, tyrosine phosphatases that dephosphorylate the insulin receptor (IR) are potential therapeutic targets. The low-molecular-weight protein tyrosine phosphatase (LMPTP) is a proposed IR phosphatase, yet its role in insulin signaling in vivo has not been defined. Here we show that global and liver-specific LMPTP deletion protects mice from high-fat diet-induced diabetes without affecting body weight. To examine the role of the catalytic activity of LMPTP, we developed a small-molecule inhibitor with a novel uncompetitive mechanism, a unique binding site at the opening of the catalytic pocket, and an exquisite selectivity over other phosphatases...
March 27, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28345832/metformin-inhibits-migration-and-invasion-of-cholangiocarcinoma-cells
#3
Son Xuan Trinh, Huyen Thi Bich Nguyen, Kween Saimuang, Virapong Prachayasittikul, Waraporn Chan On
Background: Metformin is an oral anti-diabetic agent that has been widely prescribed for treatment of type II diabetes. Anti-cancer properties of metformin have been revealed for numerous human malignancies including cholangiocarcinoma (CCA) with anti-proliferative effects in vitro. However, effects on CCA cell migration and invasion have not been fully investigated. The present study aimed to explore the inhibitory effects of metformin on motility, migration and invasion of the CCA cell line HuCCT1, and examine molecular mechanisms underlying metformin effects...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28342806/molecular-regulation-of-mitochondrial-dynamics-in-cardiac-disease
#4
REVIEW
Jinliang Nan, Wei Zhu, M S Rahman, Mingfei Liu, Dan Li, Shengan Su, Na Zhang, Xinyang Hu, Hong Yu, Mahesh P Gupta, Jian''an Wang
Mitochondrial homeostasis is critical for keeping functional heart in response to metabolic or environmental stresses. Mitochondrial fission and fusion (mitochondrial dynamics) play essential roles in maintaining mitochondrial homeostasis, defects in mitochondrial dynamics lead to cardiac diseases such as ischemia-reperfusion injury (IRI), heart failure and diabetic cardiomyopathy. Mitochondrial dynamics is determined by mitochondrial fission and fusion proteins, including OPA1, mitofusins and Drp1. These proteins are tightly regulated by a series of signaling pathways through different aspects such as transcription, post translation modifications (PTMs) and proteasome-dependent protein degradation...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342180/metabolic-syndrome-in-patients-on-first-line-antiretroviral-therapy-containing-zidovudine-or-tenofovir-in-rural-lesotho-southern-africa
#5
Niklaus Daniel Labhardt, Urs Franz Müller, Isaac Ringera, Jochen Ehmer, Mokete M Motlatsi, Karolin Pfeiffer, Michael A Hobbins, Josephine A Muhairwe, Juergen Muser, Christoph Hatz
OBJECTIVE: To assess the prevalence of metabolic syndrome (MetS) among patients in rural Lesotho who are taking first-line anti-retroviral therapy (ART) containing either zidovudine or tenofovir disoproxil. METHODS: Cross-sectional survey in 10 facilities in two districts in Lesotho of adult (≥16 years) patients on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART for ≥6 months. MetS was defined according to the International Diabetes Federation criteria...
March 25, 2017: Tropical Medicine & International Health: TM & IH
https://www.readbyqxmd.com/read/28341808/protein-coalation-a-redox-regulated-protein-modification-by-coenzyme-ain-mammalian-cells
#6
Yugo Tsuchiya, Sew Peak-Chew, Clare Newell, Sheritta Miller-Aidoo, Sriyash Mangal, Alexander Zhyvoloup, Jovana Baković, Oksana Malanchuk, Gonçalo Pereira, Vassilios Kotiadis, Gyorgy Szabadkai, Michael Duchen, Mark Campbell, Sergio Rodriguez Cuenca, Antonio Vidal-Puig, Andrew James, Michael P Murphy, Valeriy Filonenko, Mark Skehel, Ivan Gout
Coenzyme A (CoA) is an obligatory cofactor in all branches of life. CoA and its derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. Abnormal biosynthesis and homeostasis of CoA and its derivatives have been associated with various human pathologies, including cancer, diabetes and neurodegeneration. Using an anti-CoA monoclonal antibody and mass spectrometry we identified a wide range of cellular proteins which are modified by covalent attachment of CoA to cysteine thiols (CoAlation)...
March 24, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28341536/the-role-of-cpla2-in-methylglyoxal-induced-cell-apoptosis-of-huvecs
#7
Jie Yuan, Chao Zhu, Yali Hong, Zongxing Sun, Xianjun Fang, Biao Wu, Shengnan Li
Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is mainly formed as a byproduct of glycolysis. Elevated MGO level is known to induce apoptosis of vascular endothelial cells, which is implicated with progression of atherosclerosis and diabetic complications. However, the underlying mechanisms have not been exhaustively investigated yet. Here, we further characterized the mechanisms how MGO induced apoptosis in human umbilical vein endothelial cells (HUVECs). Our data revealed that cytosolic phospholipase A2 (cPLA2) played an important role in MGO-induced cell apoptosis...
March 21, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28338987/gamma-glutamyltransferase-levels-prediabetes-and-type-2-diabetes-a-mendelian-randomization-study
#8
Jana Nano, Taulant Muka, Symen Ligthart, Albert Hofman, Sarwa Darwish Murad, Harry LA Janssen, Oscar H Franco, Abbas Dehghan
Background: High levels of serum gamma-glutamyltransferase (GGT) are associated with increased risk of prediabetes and type 2 diabetes in observational studies. It is unclear whether this relationship is causal, arises from residual confounding or is a consequence of reverse causation. Methods: We used data from a prospective population-based cohort study, compromising 8611 individuals without diabetes at baseline. Cox proportional hazard models were used to study the association between serum GGT levels and incident prediabetes and diabetes...
March 13, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28338308/penile-alterations-at-early-stage-of-type-1-diabetes-in-rats
#9
Mingfang Tao, Cemal Tasdemir, Seda Tasdemir, Ali Shahabi, Guiming Liu
OBJECTIVE: Diabetes affects the erectile function significantly. However, the penile alterations in the early stage of diabetes in experimental animal models have not been well studied. We examined the changes of the penis and its main erectile components in diabetic rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 2 groups: streptozotocin (STZ)-induced diabetics and age-matched controls. Three or nine weeks after diabetes induction, the penis was removed for immunohistochemical staining of smooth muscle and neuronal nitric oxide synthase (nNOS) in midshaft penile tissues...
March 24, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/28338045/abnormal-levels-of-histone-methylation-in-the-retinas-of-diabetic-rats-are-reversed-by-minocycline-treatment
#10
Wenjun Wang, Simone Sidoli, Wenquan Zhang, Qing Wang, Leilei Wang, Ole N Jensen, Lin Guo, Xiaolu Zhao, Ling Zheng
In this study we quantified the alterations of retinal histone post-translational modifications (PTMs) in diabetic rats using a liquid chromatography - tandem mass spectrometry (LC-MS/MS) approach. Some diabetic rats were subsequently treated with minocycline, a tetracycline antibiotic, which has been shown to inhibit the diabetes-induced chronic inflammation in the retinas of rodents. We quantified 266 differentially modified histone peptides, including 48 out of 83 methylation marks with significantly different abundancein retinas of diabetic rats as compared to non-diabetic controls...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28335557/ros-production-and-erk-activity-are-involved-in-the-effects-of-d-%C3%AE-hydroxybutyrate-and-metformin-in-a-glucose-deficient-condition
#11
Santosh Lamichhane, Tonking Bastola, Ramesh Pariyar, Eun-Sol Lee, Ho-Sub Lee, Dae Ho Lee, Jungwon Seo
Hypoglycemia, a complication of insulin or sulfonylurea therapy in diabetic patients, leads to brain damage. Furthermore, glucose replenishment following hypoglycemic coma induces neuronal cell death. In this study, we investigated the molecular mechanism underlying glucose deficiency-induced cytotoxicity and the protective effect of d-β-hydroxybutyrate (D-BHB) using SH-SY5Y cells. The cytotoxic mechanism of metformin under glucose deficiency was also examined. Cell viability under 1 mM glucose (glucose deficiency) was significantly decreased which was accompanied by increased production of reactive oxygen species (ROS) and decreased phosphorylation of extracellular signal-regulated kinase (ERK) and glycogen synthase 3 (GSK3β)...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28335416/supplementation-with-phycocyanobilin-citrulline-taurine-and-supranutritional-doses-of-folic-acid-and-biotin-potential-for-preventing-or-slowing-the-progression-of-diabetic-complications
#12
Mark F McCarty
Oxidative stress, the resulting uncoupling of endothelial nitric oxide synthase (eNOS), and loss of nitric oxide (NO) bioactivity, are key mediators of the vascular and microvascular complications of diabetes. Much of this oxidative stress arises from up-regulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Phycocyanobilin (PhyCB), the light-harvesting chromophore in edible cyanobacteria such as spirulina, is a biliverdin derivative that shares the ability of free bilirubin to inhibit certain isoforms of NADPH oxidase...
March 14, 2017: Healthcare (Basel, Switzerland)
https://www.readbyqxmd.com/read/28334683/combined-metformin-and-insulin-treatment-reverses-metabolically-impaired-omental-adipogenesis-and-accumulation-of-4-hydroxynonenal-in-obese-diabetic-patients
#13
Morana Jaganjac, Shamma Almuraikhy, Fatima Al-Khelaifi, Mashael Al-Jaber, Moataz Bashah, Nayef A Mazloum, Kamelija Zarkovic, Neven Zarkovic, Georg Waeg, Wael Kafienah, Mohamed A Elrayess
OBJECTIVE: Obesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype. METHODS: OM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery...
March 16, 2017: Redox Biology
https://www.readbyqxmd.com/read/28331489/reversible-atrial-fibrillation-following-crotalinae-envenomation
#14
Dan Quan, Kenneth Zurcher
BACKGROUND: Cardiotoxicity is a documented complication of Crotalinae envenomation. Reported cardiac complications following snake envenomation have included acute myocardial infarction, electrocardiogram abnormalities and arrhythmias. Few reports exist describing arrhythmia induced by viper envenomation and to our knowledge none describe arrhythmia induced by Crotalinae envenomation. This report concerns the first known case of atrial fibrillation precipitated by rattlesnake bite. CASE PRESENTATION: A 73-year-old Caucasian man with a past medical history of hypertension, hyperlipidemia, type 1 diabetes mellitus, and a baseline first-degree atrioventricular block presented to the emergency department following a rattlesnake bite to his left lower leg...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28330852/a-controlled-release-mitochondrial-protonophore-reverses-hypertriglyceridemia-nonalcoholic-steatohepatitis-and-diabetes-in-lipodystrophic-mice
#15
Abudukadier Abulizi, Rachel J Perry, João Paulo G Camporez, Michael J Jurczak, Kitt Falk Petersen, Patricia Aspichueta, Gerald I Shulman
Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes...
March 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28324804/high-density-lipoprotein-immunomodulates-the-functional-activities-of-macrophage-and-cytokines-produced-during-ex-vivo-macrophage-cd4-t-cell-crosstalk-at-the-recent-onset-human-type-1-diabetes
#16
Ibtissem Benghalem, Warda Meziane, Zeyneb Hadjidj, Lamia Ysmail-Dahlouk, Ahmed Belamri, Kheira Mouhadjer, Mourad Aribi
BACKGROUND: Both CD4(+) T cells and macrophages are mainly involved in the autoimmune-mediated β-cells destruction in type 1 diabetes (T1D). The aim of this study was to examine the effect of HDL on functional activities of macrophage and its ability to regulate the production of cytokines in autologous mixed macrophage/CD4(+) T cells at the recent-onset human type 1 diabetes. METHODS: Cell samples were isolated from volunteers with recent-onset T1D or healthy controls...
March 16, 2017: Cytokine
https://www.readbyqxmd.com/read/28324172/enzymes-involved-in-branched-chain-amino-acid-metabolism-in-humans
#17
REVIEW
María M Adeva-Andany, Laura López-Maside, Cristóbal Donapetry-García, Carlos Fernández-Fernández, Cristina Sixto-Leal
Branched-chain amino acids (leucine, isoleucine and valine) are structurally related to branched-chain fatty acids. Leucine is 2-amino-4-methyl-pentanoic acid, isoleucine is 2-amino-3-methyl-pentanoic acid, and valine is 2-amino-3-methyl-butanoic acid. Similar to fatty acid oxidation, leucine and isoleucine produce acetyl-coA. Additionally, leucine generates acetoacetate and isoleucine yields propionyl-coA. Valine oxidation produces propionyl-coA, which is converted into methylmalonyl-coA and succinyl-coA. Branched-chain aminotransferase catalyzes the first reaction in the catabolic pathway of branched-chain amino acids, a reversible transamination that converts branched-chain amino acids into branched-chain ketoacids...
March 21, 2017: Amino Acids
https://www.readbyqxmd.com/read/28322965/inhibitory-effect-of-hesperetin-on-%C3%AE-glucosidase-molecular-dynamics-simulation-integrating-inhibition-kinetics
#18
Yan Gong, Xiu-Yuan Qin, Yuan-Yuan Zhai, Hao Hao, Jinhyuk Lee, Yong-Doo Park
The α-glucosidase inhibitor is of interest to researchers due to its association with type-2 diabetes treatment. Hesperetin is a flavonoid with natural antioxidant properties. This paper presents an evaluation on the effects of hesperetin on α-glucosidase via inhibitory kinetics using a Molecular Dynamics (MD) simulation integration method. Due to the antioxidant properties of hesperetin, it reversibly inhibits α-glucosidase in a slope-parabolic mixed-type manner (IC50=0.38±0.05mM; Kslope=0.23±0.01mM), accompanied by tertiary structural changes...
March 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28321898/a-generalized-mixture-model-applied-to-diabetes-incidence-data
#19
Daiane Aparecida Zuanetti, Luis Aparecido Milan
We present a generalization of the usual (independent) mixture model to accommodate a Markovian first-order mixing distribution. We propose the data-driven reversible jump, a Markov chain Monte Carlo (MCMC) procedure, for estimating the a posteriori probability for each model in a model selection procedure and estimating the corresponding parameters. Simulated datasets show excellent performance of the proposed method in the convergence, model selection, and precision of parameters estimates. Finally, we apply the proposed method to analyze USA diabetes incidence datasets...
March 21, 2017: Biometrical Journal. Biometrische Zeitschrift
https://www.readbyqxmd.com/read/28320859/2-arachidonoylglycerol-ameliorates-inflammatory-stress-induced-insulin-resistance-in-cardiomyocytes
#20
Dipanjan Chanda, Yvonne Oligschlaeger, Ilvy Geraets, Yilin Liu, Xiaoqing Zhu, Jieyi Li, Miranda Nabben, Will Coumans, Joost J F P Luiken, Jan F C Glatz, Dietbert Neumann
Several studies have linked impaired glucose uptake and insulin resistance (IR) to functional impairment of the heart. Recently, endocannabinoids have been implicated in cardiovascular disease. However, the mechanisms involving endocannabinoid signaling, glucose uptake and IR in cardiomyocytes are understudied. Here, we report the endocannabinoid 2-Arachidonoylglycerol (2-AG) via stimulation of cannabinoid type-1 (CB1) receptor and Ca2+/Calmodulin-dependent protein kinase β (CaMKKβ) activates AMPK leading to increased glucose uptake...
March 20, 2017: Journal of Biological Chemistry
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