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https://www.readbyqxmd.com/read/27932386/aberrant-expression-of-fbxo2-disrupts-glucose-homeostasis-through-ubiquitin-mediated-degradation-of-insulin-receptor-in-obese-mice
#1
Bin Liu, Han Lu, Duanzhuo Li, Xuelian Xiong, Lu Gao, Zhixiang Wu, Yan Lu
Insulin resistance is a critical factor in the development of metabolic disorders, including type 2 diabetes (T2DM). However, its molecular mechanisms remain incompletely understood. In the present study, we found that F-box only protein 2 (FBXO2), a substrate recognition component of SKP1-Cullin1-F-box protein (SCF) E3 ubiquitin ligase complex, were up-regulated in livers of obese mice. Furthermore, using a protein purification approach combined with high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS), we carried out a system-wide screening of FBXO2 substrates, in which insulin receptor (IR) was identified as a substrate for FBXO2...
December 8, 2016: Diabetes
https://www.readbyqxmd.com/read/27927630/inactive-matrix-gla-protein-and-arterial-stiffness-in-type-2-diabetes-mellitus
#2
Mayank Sardana, Izzah Vasim, Swapna Varakantam, Uzma Kewan, Ali Tariq, Maheshwara R Koppula, Amer Ahmed Syed, Melissa Beraun, Nadja E A Drummen, Cees Vermeer, Scott R Akers, Julio A Chirinos
BACKGROUND: Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protein (MGP) is an inhibitor of vascular calcification. Activation of MGP is vitamin K dependent. We hypothesized that levels of inactive MGP (dephospho-uncarboxylated MGP; dp-ucMGP) are related to arterial stiffness in type 2 diabetes...
December 7, 2016: American Journal of Hypertension
https://www.readbyqxmd.com/read/27926736/structure-of-cc-chemokine-receptor-2-with-orthosteric-and-allosteric-antagonists
#3
Yi Zheng, Ling Qin, Natalia V Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J Cherney, Percy Carter, Dean Stamos, Ruben Abagyan, Vadim Cherezov, Raymond C Stevens, Adriaan P IJzerman, Laura H Heitman, Andrew Tebben, Irina Kufareva, Tracy M Handel
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27925683/inorganic-polyphosphate-a-key-modulator-of-inflammation
#4
REVIEW
Seyed Mahdi Hassanian, Amir Avan, Abdolreza Ardeshirylajimi
Inorganic polyphosphate (PolyP) is a molecule with prothrombotic and proinflammatory properties in blood. PolyP activates the NF-κB signaling pathway, increases the expression of cell surface adhesion molecules and disrupts the vascular barrier integrity of endothelial cells. PolyP-induced NF-κB activation and vascular hyperpermeability are regulated by the mTORC1 and mTORC2 pathways, respectively. Through interaction with RAGE and P2Y1 receptors, PolyP dramatically amplifies the proinflammatory responses of nuclear proteins...
December 7, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27921438/-heterogeneity-of-childhood-diabetes-and-its-therapeutic-implications
#5
Zdeněk Šumník, Štěpánka Průhová, Ondřej Cinek
The prevalence of diabetes in Czech children is 1 : 500-1 000. Its incidence rose about threefold over the past 25 years. Type 1 diabetes is the prevailing form of diabetes in childhood, but also monogenic forms are frequently diagnosed. The occurrence of type 2 diabetes is still marginal in Czech children, with a relative proportion of less than 1 % of all diabetic children. Etiological diagnosis is the basic prerequisite of an effective diabetes treatment. In this review we present novel aspects on etiology and therapy of diabetes diagnosed in childhood and adolescence...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27921359/modulation-of-vegf-signaling-in-a-mouse-model-of-diabetes-by-xanthohumol-and-8-prenylnaringenin-unveiling-the-angiogenic-paradox-and-metabolism-interplay
#6
Raquel Costa, Ilda Rodrigues, Luísa Guardão, Joana Quelhas Lima, Emília Sousa, Raquel Soares, Rita Negrão
SCOPE: Imbalance in kidney and heart neovascularization is common in type2 Diabetes (T2DM) patients. Nevertheless, the mechanisms governing this angiogenic paradox have not been elucidated. Xanthohumol (XN) and 8-prenylnaringenin (8PN) beer polyphenols modulate angiogenesis, being thus targets for T2DM-related complications. Our work examined whether polyphenols consumption affects angiogenic paradox and metabolism in a T2DM mouse model. METHODS AND RESULTS: An increase in kidney and a reduction in left ventricle (LV) microvessels of diabetic C57Bl/6 mice were observed...
December 6, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27916644/targeted-mitochondrial-uncoupling-beyond-ucp1-the-fine-line-between-death-and-metabolic-health
#7
REVIEW
Mario Ost, Susanne Keipert, Susanne Klaus
In the early 1930s, the chemical uncoupling agent 2,4-dinitrophenol (DNP) was promoted for the very first time as a powerful and effective weight loss pill but quickly withdrawn from the market due to its lack of tissue-selectivity with resulting dangerous side effects, including hyperthermia and death. Today, novel mitochondria- or tissue-targeted chemical uncouplers with higher safety and therapeutic values are under investigation in order to tackle obesity, diabetes and fatty liver disease. Moreover, in the past 20 years, transgenic mouse models were generated to understand the molecular and metabolic consequences of targeted uncoupling, expressing functional uncoupling protein 1 (UCP1) ectopically in white adipose tissue or skeletal muscle...
December 1, 2016: Biochimie
https://www.readbyqxmd.com/read/27915042/non-coding-rnas-and-berberine-a-new-mechanism-of-its-anti-diabetic-activities
#8
REVIEW
Wenguang Chang
Type 2 Diabetes (T2D) is a metabolic disease with high mortality and morbidity. Non-coding RNAs, including small and long non-coding RNAs, are a novel class of functional RNA molecules that regulate multiple biological functions through diverse mechanisms. Studies in the last decade have demonstrated that non-coding RNAs may represent compelling therapeutic targets and play important roles in regulating the course of insulin resistance and T2D. Berberine, a plant-based alkaloid, has shown promise as an anti-hyperglycaemic, anti-hyperlipidaemic agent against T2D...
December 1, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27914709/podocyte-specific-chemokine-c-c-motif-receptor-2%C3%A2-overexpression-mediates-diabetic-renal-injury-in%C3%A2-mice
#9
Hanning You, Ting Gao, Wesley M Raup-Konsavage, Timothy K Cooper, Sarah K Bronson, W Brian Reeves, Alaa S Awad
Inflammation is a central pathophysiologic mechanism that contributes to diabetes mellitus and diabetic nephropathy. Recently, we showed that macrophages directly contribute to diabetic renal injury and that pharmacological blockade or genetic deficiency of chemokine (C-C motif) receptor 2 (CCR2) confers kidney protection in diabetic nephropathy. However, the direct role of CCR2 in kidney-derived cells such as podocytes in diabetic nephropathy remains unclear. To study this, we developed a transgenic mouse model expressing CCR2 specifically in podocytes (Tg[NPHS2-Ccr2]) on a nephropathy-prone (DBA/2J) and CCR2-deficient (Ccr2(-/-)) background with heterozygous Ccr2(+/-) littermate controls...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27913654/novel-small-molecule-jp-153-targets-the-src-fak-paxillin-signaling-complex-to-inhibit-vegf-induced-retinal-angiogenesis
#10
Jordan J Toutounchian, Jayaprakash Pagadala, Duane D Miller, Jerome Baudry, Frank Park, Edward Chaum, Charles R Yates
Targeting vascular endothelial growth factor (VEGF) is a common treatment strategy for neovascular eye disease, a major cause of vision loss in diabetic retinopathy and age-related macular degeneration. However, the decline in clinical efficacy over time in many patients suggests that monotherapy of anti-VEGF protein therapeutics may benefit from adjunctive treatments. Our previous work has shown that through decreased activation of the cytoskeletal protein paxillin, growth factor-induced ischemic retinopathy in the murine oxygen-induced retinopathy model could be inhibited...
January 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/27913625/absence-of-mir-146a-in-podocytes-increases-risk-of-diabetic-glomerulopathy-via-upregulation-of-erbb4-and-notch-1
#11
Ha Won Lee, Samia Q Khan, Shehryar Khaliqdina, Mehmet M Altintas, Florian Grahammer, Jimmy L Zhao, Kwihey Koh, Nicholas J Tardi, Mohd Hafeez Faridi, Terese Geraghty, David J Cimbaluk, Katalin Susztak, Luis F Moita, David Baltimore, Pierre-Louis Tharaux, Tobias B Huber, Matthias Kretzler, Markus Bitzer, Jochen Reiser, Vineet Gupta
Podocyte injury is an early event in diabetic kidney disease and is a hallmark of glomerulopathy. MicroRNA-146a (miR-146a) is highly expressed in many cell types under homeostatic conditions, and plays an important anti-inflammatory role in myeloid cells. However, its role in podocytes is unclear. Here, we show that miR-146a expression levels decrease in the glomeruli of patients with type 2 diabetes (T2D), which correlates with increased albuminuria and glomerular damage. MiR-146a levels are also significantly reduced in the glomeruli of albuminuric BTBR ob/ob mice, indicating its significant role in maintaining podocyte health...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27910739/overview-on-therapeutic-applications-of-microparticulate-drug-delivery-systems
#12
Swarna Bale, Amit Khurana, A Shiva Shankar Reddy, Mandip Singh, Chandraiah Godugu
Research in novel drug delivery systems is being explored competitively in order to attain maximum therapeutic effect while minimizing the adverse effects. Despite several advancements in pharmaceutical formulations, one of the major challenges still persisting is sustained drug release. Microencapsulation enacts as an intelligent approach with a strong therapeutic impact and is in demand globally in medical technology due to its specific and attractive properties, including biocompatibility, stability, target specificity, uniform encapsulation, better compliance, and controlled and sustained release patterns that are responsible for diminishing the toxicity and dosage frequency...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27908424/first-comprehensive-study-on-total-contents-and-hot-water-extractable-fraction-of-selected-elements-in-19-medicinal-plants-from-various-locations-in-nyamira-county-kenya
#13
Volker Nischwitz, Richard Mogwasi, Salim Zor, Zachary Getenga, David K Kariuki, Klaus Günther
A large number of medicinal plants is traditionally known in Kenya and used for treatment of various diseases, for example diabetes, where metals are supposed to be involved in pathogenesis and therapy. Therefore, detailed investigation of the concentration of a large number of metals in medicinal plants is required for improved understanding and optimisation of the therapeutic role of metals and also to exclude potentially toxic effects. Our study focused on the determination of 30 selected elements in 19 medicinal plant species each collected from 3 sampling locations in Nyamira County, Kenya...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27904096/development-and-analysis-of-novel-therapeutic-targets-to-improve-pancreatic-%C3%AE-cell-function-in-type-2-diabetes
#14
Yukiko K Kaneko
 Pancreatic β-cell dysfunction is a major feature of type 2 diabetes. Therefore maintenance of β-cell function is essential to preventing the onset and progression of type 2 diabetes. To elucidate the mechanisms underlying the regulation of insulin secretion and β-cell survival, we particularly focused on the roles of gasotransmitters in pancreatic β-cells. Nitric oxide (NO) and hydrogen sulfide (H2S) are recognized as toxic gases. However, they are also vital physiological and pathophysiological mediators in various cell types...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/27901270/adipose-tissue-inflammation-by-intermittent-hypoxia-mechanistic-link-between-obstructive-sleep-apnoea-and-metabolic-dysfunction
#15
Silke Ryan
Obstructive sleep apnoea (OSA) is a highly prevalent condition and recognized as a major public health burden conveying a significant risk of cardiometabolic diseases and mortality. Type 2 diabetes (T2D), insulin resistance (IR) and glucose tolerance are common in subjects with OSA and this association is at least in part independent of the effects of obesity. Continuous positive airway pressure (CPAP) is the treatment of choice for the majority of patients with OSA but the benefit of CPAP on glycaemic health is uncertain...
November 29, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27899481/hznt8-slc30a8-transgenic-mice-which-overexpress-the-r325w-polymorph-have-reduced-islet-zn2-and-proinsulin-levels-increased-glucose-tolerance-after-a-high-fat-diet-and-altered-levels-of-pancreatic-zinc-binding-proteins
#16
Li Li, Shi Bai, Christian T Sheline
Zinc is involved in both type-1 (T1DM) and type-2 (T2DM) diabetes. The wildtype (WT) form of the beta-cell specific Zn(2+) transporter, ZNT8, is linked to T2DM susceptibility. ZnT8 null mice have a mild phenotype with a slight decrease in glucose tolerance, whereas patients with the ZnT8 R325W polymorphism (rs13266634) have decreased proinsulin staining and susceptibility to T2DM. We measured zinc, insulin, and proinsulin stainings, and IPGTT in transgenic mice overexpressing hZnT8 WT or hZnT8 R325W fed a normal or high fat diet (HFD)...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27899023/ghrelin-function-in-human-obesity-and-type-2-diabetes-a-concise-review
#17
REVIEW
R Churm, J S Davies, J W Stephens, S L Prior
The 28 amino acid hormone, ghrelin, has been found to have various effects on metabolism. This review will focus on the pathways integrated into ghrelin's effect within the hypothalamus, pancreas and adipocytes. The identification of molecules and pathways that regulate ghrelin-mediated lipid retention could establish new mechanisms underlying cellular energy homeostasis. The impact of acyl-ghrelin on glucose metabolism and lipid homeostasis may allow for novel preventative or early intervention therapeutic strategies to treat obesity related type 2 diabetes and associated metabolic dysfunction...
November 29, 2016: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27896306/data-for-increased-rho-kinase-activity-in-type-2-diabetic-patients
#18
Lei Liu, Lun Tan, Jinsheng Lai, Sheng Li, Dao Wen Wang
The data presented in this article are related to the research article entitled "Enhanced Rho-Kinase Activity: Pathophysiological Relevance in Type 2 Diabetes" [1]. Rho-Kinase has attracted a great deal of interest as a novel therapeutic target in cardiovascular diseases. These data describe the observed relationship of Rho-Kinase activity with type 2 diabetic patients. Rho-Kinase activity is determined by immunoblotting of peripheral blood leukocytes with the Phospho-Thr853 in the myosin-binding subunit of myosin light-chain phosphatase...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27895821/implanting-1-1b4-human-%C3%AE-cell-pseudoislets-improves-glycaemic-control-in-diabetic-severe-combined-immune-deficient-mice
#19
Alastair D Green, Srividya Vasu, Neville H McClenaghan, Peter R Flatt
AIM: To investigate the potential of implanting pseudoislets formed from human insulin-releasing β-cell lines as an alternative to islet transplantation. METHODS: In this study, the anti-diabetic potential of novel human insulin releasing 1.1B4 β-cells was evaluated by implanting the cells, either as free cell suspensions, or as three-dimensional pseudoislets, into the subscapular region of severe combined immune deficient mice rendered diabetic by single high-dose administration of streptozotocin...
November 15, 2016: World Journal of Diabetes
https://www.readbyqxmd.com/read/27895388/acetate-alters-expression-of-genes-involved-in-beige-adipogenesis-in-3t3-l1-cells-and-obese-kk-ay-mice
#20
Satoko Hanatani, Hiroyuki Motoshima, Yuki Takaki, Shuji Kawasaki, Motoyuki Igata, Takeshi Matsumura, Tatsuya Kondo, Takafumi Senokuchi, Norio Ishii, Junji Kawashima, Daisuke Kukidome, Seiya Shimoda, Takeshi Nishikawa, Eiichi Araki
The induction of beige adipogenesis within white adipose tissue, known as "browning", has received attention as a novel potential anti-obesity strategy. The expression of some characteristic genes including PR domain containing 16 is induced during the browning process. Although acetate has been reported to suppress weight gain in both rodents and humans, its potential effects on beige adipogenesis in white adipose tissue have not been fully characterized. We examined the effects of acetate treatment on 3T3-L1 cells and in obese diabetic KK-Ay mice...
November 2016: Journal of Clinical Biochemistry and Nutrition
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