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Beta cell mass

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https://www.readbyqxmd.com/read/28728159/oxamate-enhances-the-anti-inflammatory-and-insulin-sensitizing-effects-of-metformin-in-diabetic-mice
#1
Mu-Chao Wu, Wei-Ran Ye, Yi-Jia Zheng, Shan-Shan Zhang
Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice...
July 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28721437/erk1-is-dispensable-for-mouse-pancreatic-beta-cell-function-but-is-necessary-for-glucose-induced-full-activation-of-msk1-and-creb
#2
Michele Leduc, Joy Richard, Safia Costes, Dany Muller, Annie Varrault, Vincent Compan, Julia Mathieu, Jean-François Tanti, Gilles Pagès, Jacques Pouyssegur, Gyslaine Bertrand, Stéphane Dalle, Magalie A Ravier
AIMS/HYPOTHESIS: Insufficient insulin secretion from pancreatic beta cells, which is associated with a decrease in beta cell mass, is a characteristic of type 2 diabetes. Extracellular signal-related kinase 1 and 2 (ERK1/2) inhibition in beta cells has been reported to affect insulin secretion, gene transcription and survival, although whether ERK1 and ERK2 play distinct roles is unknown. The aim of this study was to assess the individual roles of ERK1 and ERK2 in beta cells using ERK1 (also known as Mapk3)-knockout mice (Erk1 (-/-) mice) and pharmacological approaches...
July 18, 2017: Diabetologia
https://www.readbyqxmd.com/read/28713332/childhood-maltreatment-is-an-independent-risk-factor-for-prediabetic-disturbances-in-glucose-regulation
#3
Li Li, W Timothy Garvey, Barbara A Gower
AIMS: Childhood maltreatment (CM) is shown to be associated with obesity and depression. However, the relationship of CM to prediabetic state is much less studied. We tested the hypothesis that CM increases the risk for prediabetic state due to glucose intolerance, reduced insulin sensitivity, and beta cell function. METHODS: Oral glucose tolerance test (OGTT)-derived metabolic parameters of glucose tolerance, insulin sensitivity, and beta cell function were measured in 121 participants aged 19-60 years...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28710530/proteomic-characterisation-reveals-active-wnt-signalling-by-human-multipotent-stromal-cells-as-a-key-regulator-of-beta-cell-survival-and-proliferation
#4
Miljan Kuljanin, Gillian I Bell, Stephen E Sherman, Gilles A Lajoie, David A Hess
AIMS/HYPOTHESIS: Novel strategies to stimulate the expansion of beta cell mass in situ are warranted for diabetes therapy. The aim of this study was to elucidate the secretome of human bone marrow (BM)-derived multipotent stromal cells (MSCs) with documented islet regenerative paracrine function. We hypothesised that regenerative MSCs will secrete a unique combination of protein factors that augment islet regeneration. METHODS: Human BM-derived MSCs were examined for glucose-lowering capacity after transplantation into streptozotocin-treated NOD/severe combined immunodeficiency (SCID) mice and segregated into samples with regenerative (MSC(R)) vs nonregenerative (MSC(NR)) capacity...
July 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/28702205/association-of-arsenobetaine-with-beta-cell-function-assessed-by-homeostasis-model-assessment-homa-in-nondiabetic-koreans-data-from-the-fourth-korea-national-health-and-nutrition-examination-survey-knhanes-2008-2009
#5
Kiook Baek, Namhoon Lee, Insung Chung
BACKGROUND: Arsenic is known as an endocrine disruptor that people are exposed to through various sources such as drinking water and indigestion of marine products. Although some epidemiological and animal studies have reported a correlation between arsenic exposure and diabetes development, there are limited studies regarding the toxic effects of organic arsenic including arsenobetaine on the human body. Here, we analyzed the association between urine arsenobetaine and the homeostasis model assessment of β-cell function (HOMA-β), which is an index for predicting diabetes development and reflecting the function of pancreatic β-cells...
2017: Annals of Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/28692149/animal-models-of-human-type-1-diabetes-for-evaluating-combination-therapies-and-successful-translation-to-the-patient-with-type-1-diabetes
#6
REVIEW
Sigurd Lenzen
Animal models of human type 1 diabetes will be of a great importance for the evaluation of new combination therapies with curative potential. However, reliable predictive power for successful translation to patients with type 1 diabetes is crucial. This will be particularly important in the future when evaluating success of new combination therapies which show great promise for preservation and restoration of beta cell mass and thereby reverse the type 1 diabetic hyperglycaemia. But not all spontaneous animal models are equally well suited for this purpose...
July 10, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28676760/combined-oral-administration-of-gaba-and-dpp-4-inhibitor-prevents-beta-cell-damage-and-promotes-beta-cell-regeneration-in-mice
#7
Wenjuan Liu, Dong Ok Son, Harry K Lau, Yinghui Zhou, Gerald J Prud'homme, Tianru Jin, Qinghua Wang
γ-aminobutyric acid (GABA) or glucagon-like peptide-1 based drugs, such as sitagliptin (a dipeptidyl peptidase-4 inhibitor), were shown to induce beta cell regenerative effects in various diabetic mouse models. We propose that their combined administration can bring forth an additive therapeutic effect. We tested this hypothesis in a multiple low-dose streptozotocin (STZ)-induced beta cell injury mouse model (MDSD). Male C57BL/6J mice were assigned randomly into four groups: non-treatment diabetic control, GABA, sitagliptin, or GABA plus sitagliptin...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28671821/the-t-cell-receptor-can-bind-to-the-peptide-bound-major-histocompatibility-complex-and-uncomplexed-beta-2-microglobulin-through-distinct-binding-sites
#8
Patrick Sascha Merkle, Melita Irving, Song Hongjian, Mathias Ferber, Thomas J D Jørgensen, Kirsten Scholten, Immanuel Florian Luescher, George Coukos, Vincent Zoete, Michel A Cuendet, Olivier Michielin, Kasper D Rand
T-cell receptor (TCR)-mediated recognition of peptide-bound major histocompatibility complex (pMHC) initiates an adaptive immune response against antigen-presenting target cells. The recognition events take place at the TCR-pMHC interface and their implications on TCR conformation and dynamics are controversial. Here, we have measured the time-resolved hydrogen/deuterium exchange (HDX) of a soluble TCR in the presence and absence of its cognate pMHC by mass spectrometry to delineate the impact of pMHC binding on solution-phase structural dynamics in the TCR...
July 3, 2017: Biochemistry
https://www.readbyqxmd.com/read/28662331/ultra-performance-liquid-chromatography-tandem-mass-spectrometry-method-to-determine-formaldehyde-hemoglobin-adducts-in-humans-as-biomarker-for-formaldehyde-exposure
#9
Min Yang, Maria Ospina, Chui Tse, Stephen Toth, Samuel P Caudill, Hubert Vesper
Formaldehyde (FA) is an environmental chemical classified as a human carcinogen. It is highly reactive and can bind covalently with hemoglobin (Hb) to produce Hb adducts. Measurement of these Hb adducts provides valuable information about exposure to this chemical. We developed a robust, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantifying FA-Hb adducts in red blood cells. The method measures the FA-VHLTPEEK peptide after trypic digestion. The peptide is a FA adduct at the N-terminus of the beta chain of human Hb...
June 29, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28652605/distinct-levels-of-reactive-oxygen-species-coordinate-metabolic-activity-with-beta-cell-mass-plasticity
#10
Ezzaldin Ahmed Alfar, Dilyana Kirova, Judith Konantz, Sarah Birke, Jörg Mansfeld, Nikolay Ninov
The pancreatic beta-cells control glucose homeostasis by secreting insulin in response to nutrient intake. The number of beta-cells is under tight metabolic control, as this number increases with higher nutrient intake. However, the signaling pathways matching nutrition with beta-cell mass plasticity remain poorly defined. By applying pharmacological and genetic manipulations, we show that reactive oxygen species (ROS) regulate dose-dependently beta-cell proliferation in vivo and in vitro. In particular, reducing ROS levels in beta-cells blocks their proliferation in response to nutrients...
June 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28649475/solid-pseudopapillary-tumor-of-the-pancreas-an-unusual-cause-of-abdominal-pain
#11
Talal El Imad, Fady G Haddad, Mayurathan Kesavan, Liliane Deeb, Sherif Andrawes
Solid-pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor that accounts for less than one percent of pancreatic tumors. The diagnosis could be challenging as SPN tend to manifest with nonspecific abdominal symptoms, variable radiological features, and inconsistent morphology. The cellular origin of SPN is unclear and might involve ductal, acinar and endocrine stem cells.  We report a rare case of a 27-year-old female who presented with intermittent abdominal pain for two years, associated with a decrease in appetite...
May 16, 2017: Curēus
https://www.readbyqxmd.com/read/28648619/nuclear-import-of-glucokinase-in-pancreatic-beta-cells-is-mediated-by-a-nuclear-localization-signal-and-modulated-by-sumoylation
#12
Bente Berg Johansson, Karianne Fjeld, Marie Holm Solheim, Jun Shirakawa, Enming Zhang, Magdalena Keindl, Jiang Hu, Andreas Lindqvist, Anne Døskeland, Gunnar Mellgren, Torgeir Flatmark, Pål Rasmus Njølstad, Rohit N Kulkarni, Nils Wierup, Ingvild Aukrust, Lise Bjørkhaug
The localization of glucokinase in pancreatic beta-cell nuclei is a controversial issue. Although previous reports suggest such a localization, the mechanism for its import has so far not been identified. Using immunofluorescence, subcellular fractionation and mass spectrometry, we here present evidence in support of glucokinase localization in beta-cell nuclei of human and mouse pancreatic sections, as well as in human and mouse isolated islets, and murine MIN6 cells. We have identified a conserved, seven-residue nuclear localization signal ((30)LKKVMRR(36)) in the human enzyme...
June 22, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28647906/exogenous-gdf11-induces-cardiac-and-skeletal-muscle-dysfunction-and-wasting
#13
Teresa A Zimmers, Yanling Jiang, Meijing Wang, Tiffany W Liang, Joseph E Rupert, Ernie D Au, Francesco E Marino, Marion E Couch, Leonidas G Koniaris
Growth differentiation factor 11 (GDF11), a TGF-beta superfamily member, is highly homologous to myostatin and essential for embryonic patterning and organogenesis. Reports of GDF11 effects on adult tissues are conflicting, with some describing anti-aging and pro-regenerative activities on the heart and skeletal muscle while others opposite or no effects. Herein, we sought to determine the in vivo cardiac and skeletal muscle effects of excess GDF11. Mice were injected with GDF11 secreting cells, an identical model to that used to initially identify the in vivo effects of myostatin...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28646302/t-regulatory-cells-exhibit-a-biphasic-response-to-prolonged-endurance-exercise-in-humans
#14
Tom Clifford, Matthew J Wood, Philip Stocks, Glyn Howatson, Emma J Stevenson, Catharien M U Hilkens
PURPOSE: T-regulatory cells (Tregs) are a sub-population of lymphocytes that act to suppress aberrant immune responses. We investigated changes in the numbers of naïve and terminally differentiated Tregs in the peripheral blood to establish their role in the immuno-suppressive response to prolonged exercise. METHODS: Blood was drawn from seventeen experienced runners (age 40 ± 12 years; height 1.75 ± 0.08 m; mass 71.4 ± 10.8 kg) before, ~1 h after (POST-1h), and on the day following the marathon (POST-1d)...
June 23, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28633420/pancreas-fat-and-beta-cell-mass-in-humans-with-and-without-diabetes-an-analysis-in-the-japanese-population
#15
Rie Murakami, Yoshifumi Saisho, Yuusuke Watanabe, Jun Inaishi, Tami Tsuchiya, Kinsei Kou, Seiji Sato, Minoru Kitago, Yuko Kitagawa, Taketo Yamada, Hiroshi Itoh
Context: The mechanisms by which beta cell mass is reduced in patients with type 2 diabetes (T2DM) remain unclear. It has been postulated that ectopic fat deposits in the pancreas induce beta cell apoptosis, leading to the development of diabetes. Objective: The aim of this study was to clarify the effects of intra-pancreatic fat on beta and alpha cell mass in humans with and without diabetes. Design, Subjects and Methods: Using our tissue database, pancreas sections of 72 Japanese non-diabetic (NDM) autopsy cases and 50 diabetic (DM) and 49 age- and BMI-matched NDM patients who underwent pancreatic surgery were analyzed...
June 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28628102/regulation-of-body-weight-and-energy-homeostasis-by-neuronal-cell-adhesion-molecule-1
#16
Thomas Rathjen, Xin Yan, Natalia L Kononenko, Min-Chi Ku, Kun Song, Leiron Ferrarese, Valentina Tarallo, Dmytro Puchkov, Gaga Kochlamazashvili, Sebastian Brachs, Luis Varela, Klara Szigeti-Buck, Chun-Xia Yi, Sonja C Schriever, Sudhir Gopal Tattikota, Anne Sophie Carlo, Mirko Moroni, Jan Siemens, Arnd Heuser, Louise van der Weyden, Andreas L Birkenfeld, Thoralf Niendorf, James F A Poulet, Tamas L Horvath, Matthias H Tschöp, Matthias Heinig, Mirko Trajkovski, Volker Haucke, Matthew N Poy
Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure...
June 19, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28627196/comparison-of-gene-expression-profile-between-blood-cells-and-white-adipose-tissue-of-patients-with-obesity
#17
Marcela Augusta de Souza Pinhel, Natália Yumi Noronha, Carolina Ferreira Nicoletti, Driele Cristina Gomes Quinhoneiro, Bruno Affonso Parenti Oliveira, Cristiana Cortes-Oliveira, Wilson Salgado-Junior, Wilson Araújo da Silva-Junior, Júlio Sergio Marchini, Dorotéia Rossi Silva Souza, Carla Barbosa Nonino
INTRODUCTION: Gene expression analyses from peripheral blood mononuclear cells (PBMC) and white adipose tissue are conflicting. It seems that results from single tissue are not enough to explain how changes affect humans as a complex biological system. OBJECTIVE: The aim of this study was to compare, from obesity subjects, PBMC and white adipose tissue gene expression that regulates adipogenesis (perilipin 1 [PLIN1], adrenoreceptor beta 3 [ADRB3] and peroxisome proliferator-activated receptor [PPARG2]) and the energy metabolism (uncoupling protein UCP1, UCP2 and UCP3) process...
June 5, 2017: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
https://www.readbyqxmd.com/read/28625491/insulinotropic-action-of-2-4-dinitroanilino-benzoic-acid-through-the-attenuation-of-pancreatic-beta-cell-lesions-in-diabetic-rats
#18
Humera Jahan, M Iqbal Choudhary, Mehwish Manzoor, Khalid Mohammad Khan, Shahnaz Perveen, Atta-Ur-Rahman
Beta cell destruction plays a key role in the pathogenesis of type 1 diabetes mellitus. It has also been argued that beta-cell mass is compromised in some cases of type 2 diabetes, although this is still debated. Currently, the failure of oral antidiabetic insulin secretagogue drugs to properly manage type 2 diabetes demands novel approaches for the treatment of this condition. The aim of the present study was to investigate the in vitro and in vivo antidiabetic effect in STZ-induced diabetic rats, and maximum tolerated dose (MTD) safety of novel anthranilic acid derivative, 2, 4-dinitroanilino-benzoic acid (1)...
June 15, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28617856/the-associations-between-vdr-bsmi-polymorphisms-and-risk-of-vitamin-d-deficiency-obesity-and-insulin-resistance-in-adolescents-residing-in-a-tropical-country
#19
Rayinda Rahmadhani, Nur Lisa Zaharan, Zahurin Mohamed, Foong Ming Moy, Muhammad Yazid Jalaludin
BACKGROUND: The vitamin D receptor (VDR) gene is expressed abundantly in different tissues; including adipocytes and pancreatic beta cells. The rs1544410 or BsmI single nucleotide polymorphism (SNP) in the intronic region of the VDR gene has been previously associated with vitamin D levels, obesity and insulin resistance. AIMS: This study was aimed to examine the association between BsmI polymorphism and risk of vitamin D deficiency, obesity and insulin resistance in adolescents living in a tropical country...
2017: PloS One
https://www.readbyqxmd.com/read/28598424/raptor-regulates-functional-maturation-of-murine-beta-cells
#20
Qicheng Ni, Yanyun Gu, Yun Xie, Qinglei Yin, Hongli Zhang, Aifang Nie, Wenyi Li, Yanqiu Wang, Guang Ning, Weiqing Wang, Qidi Wang
Diabetes is associated with beta cell mass loss and islet dysfunctions. mTORC1 regulates beta cell survival, proliferation and function in physiological and pathological conditions, such as pregnancy and pancreatectomy. Here we show that deletion of Raptor, which is an essential component of mTORC1, in insulin-expressing cells promotes hypoinsulinemia and glucose intolerance. Raptor-deficient beta cells display reduced glucose responsiveness and exhibit a glucose metabolic profile resembling fetal beta cells...
June 9, 2017: Nature Communications
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