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https://www.readbyqxmd.com/read/27926856/insulin-dependent-activation-of-mch-neurons-impairs-locomotor-activity-and-insulin-sensitivity-in-obesity
#1
A Christine Hausen, Johan Ruud, Hong Jiang, Simon Hess, Hristo Varbanov, Peter Kloppenburg, Jens C Brüning
Melanin-concentrating-hormone (MCH)-expressing neurons (MCH neurons) in the lateral hypothalamus (LH) are critical regulators of energy and glucose homeostasis. Here, we demonstrate that insulin increases the excitability of these neurons in control mice. In vivo, insulin promotes phosphatidylinositol 3-kinase (PI3K) signaling in MCH neurons, and cell-type-specific deletion of the insulin receptor (IR) abrogates this response. While lean mice lacking the IR in MCH neurons (IR(ΔMCH)) exhibit no detectable metabolic phenotype under normal diet feeding, they present with improved locomotor activity and insulin sensitivity under high-fat-diet-fed, obese conditions...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27925416/association-of-a-gain-of-function-variant-in-lgr4-with-central-obesity
#2
Yaoyu Zou, Tinglu Ning, Juan Shi, Maopei Chen, Lin Ding, Ya Huang, Sophie Kauderer, Min Xu, Bin Cui, Yufang Bi, Simin Liu, Jie Hong, Ruixin Liu, Guang Ning, Jiqiu Wang
OBJECTIVE: To determine the relationship of the gain-of-function variant A750T in leucine-rich repeat containing G protein-coupled receptor 4 (LGR4) with central obesity and related metabolic phenotypes. METHODS: The LGR4 A750T (c.2248 G > A) variant was detected by Sanger sequencing in a discovery young population and a validation community-based population with obesity from eastern China. Fat indices determined by anthropometry and computed tomography scans and clinical biochemical measurements were collected for association analysis...
December 7, 2016: Obesity
https://www.readbyqxmd.com/read/27925358/castration-induced-changes-in-the-expression-profiles-and-promoter-methylation-of-the-ghr-gene-in-huainan-male-pigs
#3
Jing Wang, Junfeng Chen, Jiaqing Zhang, Binwen Gao, Xianxiao Bai, Yali Lan, Ping Lin, Hongxia Guo, Yuan Gao, Baosong Xing
Castration plays a regulatory role in growth and carcass traits, particularly in fat deposition, but its molecular mechanisms are still not clear. The present study showed that castration significantly reduced the serum growth hormone and the responses of the growth hormone receptor (GHR), insulin-like growth factor 1 (IGF-I), IGF-IR and peroxisome proliferator-activated receptor gamma (PPARγ) to castration were similar in different adipose tissues. However, the GHR expression trends were opposite between the liver and the adipose tissues; bisulfite sequencing PCR (BSP) showed that its methylation in these two tissues was different...
December 7, 2016: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/27925195/palmitoleic-acid-improves-metabolic-functions-in-fatty-liver-by-ppar%C3%AE-dependent-ampk-activation
#4
Camila O Souza, Alexandre A S Teixeira, Luana A Biondo, Edson A Lima, Helena A P Batatinha, Jose C Rosa Neto
BACKGROUND: Palmitoleic acid, since described as lipokine, increases glucose uptake by modulation of 5'AMP-activated protein kinase (AMPK), as well as increasing lipolysis by activation of peroxisome proliferator-activated receptor-α (PPARα), in adipose tissue. However in liver, the effects of palmitoleic acid on glucose metabolism and the role of PPARα remain unknown. OBJECTIVE: To investigate whether palmitoleic acid improved the hepatic insulin sensitivity of obese mice...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27923977/absence-of-renal-enlargement-in-fructose-fed-proximal-tubule-select-insulin-receptor-ir-insulin-like-growth-factor-receptor-igf1r-double-knockout-mice
#5
Lijun Li, Marcus Byrd, Kwame Doh, Patrice D Dixon, Hwal Lee, Swasti Tiwari, Carolyn M Ecelbarger
The major site of fructose metabolism in the kidney is the proximal tubule (PT). To test whether insulin and/or IGF1 signaling in the PT is involved in renal structural/functional responses to dietary fructose, we bred mice with dual knockout (KO) of the insulin receptor (IR) and the IGF1 receptor (IGF1R) in PT by Cre-lox recombination, using a γ-glutamyl transferase promoter. KO mice had slightly (~10%) reduced body and kidney weights, as well as, a reduction in mean protein-to-DNA ratio in kidney cortex suggesting smaller cell size...
December 2016: Physiological Reports
https://www.readbyqxmd.com/read/27923872/dopamine-directly-increases-mitochondrial-mass-and-thermogenesis-in-brown-adipocytes
#6
Rose Kohlie, Nina Perwitz, Julia Resch, Sebastian Michael Schmid, Hendrik Lehnert, Johannes Klein, Karl Alexander Iwen
Brown adipose tissue (BAT) is key to energy homeostasis. By virtue of its thermogenic potential it may dissipate excessive energy, regulate body weight, and increase insulin sensitivity. Catecholamines are critically involved in the regulation of BAT-thermogenesis, yet research has focussed on the effects of noradrenaline and adrenaline. Some evidence suggests a role of dopamine (DA) in BAT-thermogenesis but the cellular mechanisms involved have not been addressed. We employed our extensively characterised murine brown adipocyte cells...
December 6, 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27923787/type-of-supplemented-simple-sugar-not-merely-calorie-intake-determines-adverse-effects-on-metabolism-and-aortic-function-in-female-rats
#7
Gemma Sangüesa, Sonali Shaligram, Farjana Akhter, Núria Roglans, Juan C Laguna, Roshanak Rahimian, Marta Alegret
High consumption of simple sugars causes adverse cardio-metabolic effects. We investigated the mechanisms underlying the metabolic and vascular effects of glucose or fructose intake and determined whether these effects are exclusively related to increased calorie consumption. Female Sprague-Dawley rats were supplemented with 20% w/v glucose or fructose for 2 months, and plasma analytes and aortic response to vasodilator and vasoconstrictor agents were determined. Expression of molecules associated with lipid metabolism, insulin signalling and vascular response were evaluated in hepatic and/or aortic tissues...
December 6, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27923328/modeling-stroma-induced-drug-resistance-in-a-tissue-engineered-tumor-model-of-ewing-sarcoma
#8
Marco Santoro, Brian A Menegaz, Salah-Eddine Lamhamedi-Cherradi, Eric R Molina, Danielle Wu, Waldemar Priebe, Joseph A Ludwig, Antonios G Mikos
Three-dimensional (3D) tumor models are gaining traction in the research community given their capacity to mimic aspects of the tumor microenvironment absent in monolayer systems. In particular, the ability to spatiotemporally control cell placement within ex vivo 3D systems has enabled the study of tumor-stroma interactions. Furthermore, by regulating biomechanical stimuli, one can reveal how biophysical cues affect stromal cell phenotype and how their phenotype impacts tumor drug sensitivity. Both tumor architecture and shear force have profound effects on Ewing sarcoma (ES) cell behavior and are known to elicit ligand-mediated activation of the insulin-like growth factor-1 receptor (IGF-1R), thereby mediating resistance of ES cells to IGF-1R inhibitors...
December 6, 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27922332/effect-of-moderate-and-high-intensity-chronic-exercise-on-the-pancreatic-islet-morphometry-in-healthy-rats-bdnf-receptor-participation
#9
Alberto Jiménez-Maldonado, Adolfo Virgen-Ortiz, Valery Melnikov, Alejandrina Rodríguez-Hernández, Armando Gamboa-Domínguez, Sergio Montero, Jesús Muñiz-Murguía, Mónica Lemus, Elena Roces de Álvarez-Buylla
A B S T R A C T The function and morphology of β-cells is largely dependent on insulin demand. As β-cells cover a bigger cell proportion in pancreas islets, changes of insulin producer cells affect the whole pancreatic islet morphology. Growth factors as the neurotrophins regulate the pancreas physiology, besides; physical exercise increases insulin sensitivity, and further modifies brain derived neurotrophic factor (BDNF) concentration in plasma. The aim of this study was to investigate the effects of chronic exercise (running in a treadmill for eight weeks) intensity on pancreatic islet morphometry in healthy state...
December 6, 2016: Islets
https://www.readbyqxmd.com/read/27920123/selective-enhancement-of-insulin-sensitivity-in-the-endothelium-in-vivo-reveals-a-novel-proatherosclerotic-signalling-loop
#10
Hema Viswambharan, Nadira Y Yuldasheva, Anshuman Sengupta, Helen Imrie, Matthew C Gage, Natalie J Haywood, Andrew M Walker, Anna Skromna, Natalia Makova, Stacey L Galloway, Pooja Shah, Piruthivi Sukumar, Karen E Porter, Peter J Grant, Ajay M Shah, Celio X Santos, Jing Li, David J Beech, Stephen Wheatcroft, Richard M Cubbon, Mark T Kearney
RATIONALE: In the endothelium, insulin stimulates endothelial nitric oxide synthase (eNOS) to generate the anti-atherosclerotic signalling radical NO. Insulin resistant type 2 diabetes is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear. OBJECTIVE: To answer this question we generated a mouse with endothelial cell (EC)-specific over-expression of the human insulin receptor (hIRECO) using the Tie2 promoter-enhancer...
December 5, 2016: Circulation Research
https://www.readbyqxmd.com/read/27920090/islet-derived-cd4-t-cells-targeting-proinsulin-in-human-autoimmune-diabetes
#11
Aaron W Michels, Laurie G Landry, Kristen A McDaniel, Liping Yu, Martha Campbell-Thompson, William W Kwok, Kenneth L Jones, Peter A Gottlieb, John W Kappler, Qizhi Tang, Bart O Roep, Mark A Atkinson, Clayton E Mathews, Maki Nakayama
Type 1 diabetes results from chronic autoimmune destruction of insulin-producing beta cells within pancreatic islets. While insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrating T-cells. Here we show that proinsulin peptides are targeted by islet-infiltrating T-cells from type 1 diabetes patients. We identified hundreds of T-cells from inflamed pancreatic islets of three young type 1 diabetes organ donors with a short disease duration with high risk HLA genes using a direct T-cell receptor (TCR) sequencing approach without long-term cell culture...
December 5, 2016: Diabetes
https://www.readbyqxmd.com/read/27918728/cholesterol-metabolism-in-rabbit-blastocysts-under-maternal-diabetes
#12
S Mareike Pendzialek, Maria Schindler, Torsten Plösch, Jacqueline Gürke, Elisa Haucke, Stefanie Hecht, Bernd Fischer, Anne Navarrete Santos
In the rabbit reproductive model, maternal experimentally induced insulin-dependent diabetes mellitus (expIDD) leads to accumulation of lipid droplets in blastocysts. Cholesterol metabolism is a likely candidate to explain such metabolic changes. Therefore, in the present study we analysed maternal and embryonic cholesterol concentrations and expression of related genes in vivo (diabetic model) and in vitro (embryo culture in hyperglycaemic medium). In pregnant expIDD rabbits, the serum composition of lipoprotein subfractions was changed, with a decrease in high-density lipoprotein cholesterol and an increase in very low-density lipoprotein cholesterol; in uterine fluid, total cholesterol concentrations were elevated...
December 6, 2016: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/27918077/type-2-diabetes-inhibited-human-mesenchymal-stem-cells-angiogenic-response-by-over-activity-of-the-autophagic-pathway
#13
Aysa Rezabakhsh, Omid Cheraghi, Alireza Nourazarian, Mehdi Hassanpour, Masoumeh Kazemi, Shahrooz Ghaderi, Esmaeil Faraji, Reza Rahbarghazi, Çığır Biray Avci, Bakiye Goker Bagca, Alireza Garjani
The current study aimed to address the impact of serum from type 2 diabetes patients on the angiogenic properties of human bone marrow mesenchymal stem cells and its relationship to autophagy signaling. Human primary stem cells were enriched and incubated with serum from diabetic and normal subjects for 7 days. Compared to data from the control group, diabetic serum was found to induce a higher cellular death rate (p < 0.001) and apoptotic changes (p < 0.01). We also showed that diabetic condition significantly abolished angiogenesis tube formation on Matrigel substrate, decreased cell chemotaxis (p < 0...
December 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27916275/artemisinins-target-gabaa-receptor-signaling-and-impair-%C3%AE-cell-identity
#14
Jin Li, Tamara Casteels, Thomas Frogne, Camilla Ingvorsen, Christian Honoré, Monica Courtney, Kilian V M Huber, Nicole Schmitner, Robin A Kimmel, Roman A Romanov, Caterina Sturtzel, Charles-Hugues Lardeau, Johanna Klughammer, Matthias Farlik, Sara Sdelci, Andhira Vieira, Fabio Avolio, François Briand, Igor Baburin, Peter Májek, Florian M Pauler, Thomas Penz, Alexey Stukalov, Manuela Gridling, Katja Parapatics, Charlotte Barbieux, Ekaterine Berishvili, Andreas Spittler, Jacques Colinge, Keiryn L Bennett, Steffen Hering, Thierry Sulpice, Christoph Bock, Martin Distel, Tibor Harkany, Dirk Meyer, Giulio Superti-Furga, Patrick Collombat, Jacob Hecksher-Sørensen, Stefan Kubicek
Type 1 diabetes is characterized by the destruction of pancreatic β cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types, including glucagon-producing α cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of α cells to functional β-like cells. Here, we identify artemisinins as small molecules that functionally repress Arx by causing its translocation to the cytoplasm...
November 30, 2016: Cell
https://www.readbyqxmd.com/read/27915035/hyperinsulinaemic-hypoglycaemia-in-children-and-adults
#15
REVIEW
Pratik Shah, Sofia A Rahman, Huseyin Demirbilek, Maria Güemes, Khalid Hussain
Pancreatic β cells are functionally programmed to release insulin in response to changes in plasma glucose concentration. Insulin secretion is precisely regulated so that, under normal physiological conditions, fasting plasma glucose concentrations are kept within a narrow range of 3·5-5·5 mmol/L. In hyperinsulinaemic hypoglycaemia, insulin secretion becomes dysregulated (ie, uncoupled from glucose metabolism) so that insulin secretion persists in the presence of low plasma glucose concentrations. Hyperinsulinaemic hypoglycaemia is the most common cause of severe and persistent hypoglycaemia in neonates and children...
November 30, 2016: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/27914795/insulin-use-adipokine-profiles-and-breast-cancer-prognosis
#16
Zachary A P Wintrob, Jeffrey P Hammel, Thaer Khoury, George K Nimako, Hsin-Wei Fu, Zahra S Fayazi, Dan P Gaile, Alan Forrest, Alice C Ceacareanu
BACKGROUND: Type-2 diabetes mellitus (T2DM) and breast cancer (BC) share common cytokine signaling changes resultant from adipose tissue dysfunction. This modified adipokine signaling was shown to be directly associated with changes in the body mass index (BMI) and diet and it is expected to also be influenced by T2DM pharmacotherapy. We evaluated the relationship between pre-existing diabetes treatment, circulating adipokine levels at cancer diagnosis, and long-term outcomes. METHODS: All incident BC cases were reviewed (01/01/2003-12/31/2009, N=2194)...
November 30, 2016: Cytokine
https://www.readbyqxmd.com/read/27914526/jiawei-erzhiwan-improves-menopausal-metabolic-syndrome-by-enhancing-insulin-secretion-in-pancreatic-%C3%AE-cells
#17
Xiao-Meng Wan, Mu Zhang, Pei Zhang, Zhi-Shen Xie, Feng-Guo Xu, Ping Zhou, Shi-Ping Ma, Xiao-Jun Xu
Menopausal metabolic syndrome (MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases (CVD) and type II diabetes mellitus (T2DM). Erzhiwan (EZW), composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan (JE)...
November 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27914036/prolactin-regulatory-element-binding-protein-is-involved-in-suppression-of-the-adiponectin-gene-in-vivo
#18
X Z Zhang, H Imachi, J Y Lyu, K Fukunaga, S Sato, T Ibata, T Kobayashi, T Yoshimoto, F Kikuchi, T Dong, K Murao
PURPOSE: Prolactin regulatory element-binding protein (PREB), a member of the WD-repeat protein family, has been recognized as a transcriptional factor that regulates prolactin promoter activity in the anterior pituitary of rats. PREB is expressed not only in the pituitary but also in various other tissues, including the adipose tissue. Previous studies have shown that PREB acts as a transcriptional regulator and suppresses the expression of the adiponectin gene in cultured 3T3L1 preadipocytes...
December 2, 2016: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/27913611/silent-somatotroph-tumour-revisited-from-a-study-of-80-patients-with-and-without-acromegaly-and-a-review-of-the-literature
#19
Laura Chinezu, Alexandre Vasiljevic, Jacqueline Trouillas, Marion Lapoirie, Emmanuel Jouanneau, Gérald Raverot
BACKGROUND: Silent somatotroph tumours are growth hormone (GH) immunoreactive (IR) pituitary tumours without clinical and biological signs of acromegaly. Their better characterisation is required to improve the diagnosis. MATERIALS AND METHODS: Twenty-one silent somatotroph tumours were compared to 59 somatotroph tumours with acromegaly. Tumours in each group were classified into GH and plurihormonal (GH/prolactin (PRL)/±thyroid-stimulating hormone (TSH)) and into densely granulated (DG) and sparsely granulated (SG) types...
February 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27913575/lowest-glucose-variability-and-hypoglycemia-are-observed-with-the-combination-of-a-glp-1-receptor-agonist-and-basal-insulin-variation-study
#20
Harpreet S Bajaj, Karri Venn, Chenglin Ye, Avril Patrick, Shivani Kalra, Hasnain Khandwala, Nadeem Aslam, David Twum-Barima, Ronnie Aronson
OBJECTIVE: There is a dearth of published literature comparing glucose variability (GV) between different insulin regimens in type 2 diabetes. This cohort study compares GV using continuous glucose monitoring (CGM) in patients with well-controlled type 2 diabetes using four common insulin regimens: basal insulin + oral drugs (BO), basal insulin + glucagon-like peptide 1 receptor agonist (GLP-1 RA) (BGLP), premixed insulin (PM), and basal-bolus insulin (BB). RESEARCH DESIGN AND METHODS: Consecutive patients from three endocrinology clinics who met study criteria-type 2 diabetes, age 18 to 80 years, BMI ≤ 45 kg/m(2), stable insulin regimen for a minimum of 6 months, and stable A1C value ≤7...
December 2, 2016: Diabetes Care
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