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https://www.readbyqxmd.com/read/28938487/regulation-of-endogenous-male-rodent-glp-1-secretion-and-human-islet-insulin-secretion-by-antagonism-of-somatostatin-receptor-5
#1
Thomas B Farb, Marta Adeva, Thomas J Beauchamp, Over Cabrera, David A Coates, Tamika DeShea Meredith, Brian A Droz, Alexander Efanov, James V Ficorilli, Susan L Gackenheimer, Maria A Martinez-Grau, Victoriano Molero, Gema Ruano, Michael A Statnick, Todd M Suter, Samreen K Syed, Miguel A Toledo, Francis S Willard, Xin Zhou, Krister B Bokvist, David G Barrett
Incretin and insulin responses to nutrient loads are suppressed in persons with diabetes, resulting in decreased glycemic control. Whereas agents including sulfonylureas and Dipeptidyl peptidase-4 inhibitors (DPP4i) partially reverse these effects and provide therapeutic benefit, their modes of action limit efficacy. Because somatostatin (SST) has been shown to suppress both insulin and GLP-1 secretion through the Gi-coupled SST receptor 5 (SSTR5) isoform in vitro, antagonism of SSTR5 may improve glycemic control via intervention in both pathways...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938465/serum-insulin-bioassay-reflects-insulin-sensitivity-and-requirements-in-type-1-diabetes
#2
Joseph A M J L Janssen, Gemma Llauradó, Aimee J Varewijck, Per-Henrik Groop, Carol Forsblom, Sonia Fernández-Veledo, Elisabeth S R van den Dungen, Joan Vendrell, Leo J Hofland, Hannele Yki-Järvinen
Background: Insulin resistance could increase insulin requirements in type 1 diabetes (TD1). Current insulin immunoassays do not detect insulin analogues. Kinase Insulin Receptor Activation (KIRA) bioassays specific for human insulin receptor isoforms A and B (IR-A and IR-B) permit assessment of all circulating insulin bioactivity. We studied whether IR-A and IR-B KIRA assays are related to direct measures of insulin sensitivity or insulin doses in TD1. Methods: We evaluated 31 adult patients with TD1 (age 45...
August 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938457/the-association-of-estrogen-receptor-%C3%AE-gene-variation-with-salt-sensitive-blood-pressure
#3
Worapaka Manosroi, Jia Wei Tan, Chevon M Rariy, Bei Sun, Mark O Goodarzi, Aditi R Saxena, Jonathan S Williams, Luminita H Pojoga, Jessica Lasky-Su, Jinrui Cui, Xiuqing Guo, Kent D Taylor, Yii-Der I Chen, Anny H Xiang, Willa A Hsueh, Leslie J Raffel, Thomas A Buchanan, Jerome I Rotter, Gordon H Williams, Ellen W Seely
Context: Hypertension in young women is uncommon compared to young men and older women. Estrogen appears to protect most women against hypertension with incidence increasing after menopause. Since some premenopausal women develop hypertension, estrogen may play a different role in these women. Genetic variations in the estrogen receptor (ER) are associated with cardiovascular disease. ER-β, encoded by ESR2, is the ER predominantly expressed in vascular smooth muscle. Objective: To determine an association of single nucleotide polymorphisms (SNPs) in ESR2 with salt-sensitivity of blood pressure (SSBP) and estrogen status in women...
September 5, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938455/bile-acid-alterations-are-associated-with-insulin-resistance-but-not-with-nash-in-obese-subjects
#4
Vanessa Legry, Sven Francque, Joel T Haas, An Verrijken, Sandrine Caron, Oscar Chávez-Talavera, Emmanuelle Vallez, Luisa Vonghia, Eveline Dirinck, Ann Verhaegen, Mostafa Kouach, Sophie Lestavel, Philippe Lefebvre, Luc Van Gaal, Anne Tailleux, Réjane Paumelle, Bart Staels
Context: Bile acids (BA) are signalling molecules controlling energy homeostasis which can be both toxic and protective for the liver. BA alterations have been reported in obesity, insulin resistance (IR) and non-alcoholic steatohepatitis (NASH). However whether BA alterations contribute to NASH independently of the metabolic status is unclear. Objective: To assess BA alterations associated with NASH independently of BMI and IR. Design & Setting: Patients visiting the obesity clinic of the Antwerp University Hospital (a tertiary referral facility) were recruited from 2006 to 2014...
August 4, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938451/antibody-mediated-targeting-of-the-fgfr1c-isoform-increases-glucose-uptake-in-white-and-brown-adipose-tissue-in-male-mice
#5
Jo E Lewis, Ricardo J Samms, Scott Cooper, Jeni C Luckett, Alan C Perkins, James D Dunbar, Dennis P Smith, Paul J Emmerson, Andrew C Adams, Francis J P Ebling, Kostas Tsintzas
The increased prevalence of obesity and its cardiometabolic implications demonstrates the imperative to identify novel therapeutic targets able to effect meaningful metabolic changes in this population. Antibody-mediated targeting of fibroblast growth factor receptor 1c isoform (FGFR1c) has been shown to ameliorate hyperglycaemia and protect from diet- and genetically-induced obesity in rodents and non-human primates. However, it is currently unknown which tissue(s) contribute to this glucose lowering effect...
August 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938444/lack-of-lrp5-signaling-in-osteoblasts-sensitizes-male-mice-to-diet-induced-disturbances-in-glucose-metabolism
#6
Soohyun P Kim, Julie L Frey, Zhu Li, Brian C Goh, Ryan C Riddle
Wnt signaling through the Lrp5 co-receptor regulates osteoblast maturation, matrix mineralization, and intermediary metabolism. In the mature osteoblast, signals downstream of Lrp5 are required for normal long-chain fatty acid β-oxidation and mice rendered deficient for this co-receptor in osteoblasts and osteocytes accumulate body fat with elevated serum lipid levels, but retain normal insulin sensitivity. In this study, we challenged Lrp5 mutant mice with a high fat diet to determine if they are more susceptible to diet-induced disturbances in glucose homeostasis...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938426/a-sustained-activation-of-pancreatic-nmdars-is-a-novel-factor-of-%C3%AE-cell-apoptosis-and-dysfunction
#7
Xiao-Ting Huang, Shao-Jie Yue, Chen Li, Yan-Hong Huang, Qing-Mei Cheng, Xiao-Hong Li, Cai-Xia Hao, Ling-Zhi Wang, Jian-Ping Xu, Ming Ji, Chen Chen, Dan-Dan Feng, Zi-Qiang Luo
Type 2 diabetes, which features β-cell failure, is caused by the decrease of β-cell mass and insulin secretory function. Current treatments fail to halt the decrease of functional β-cell mass. Strategies to prevent β-cell apoptosis and dysfunction are highly desirable. Recently, our group and others have reported that blockade of N-methyl-D-aspartate receptors (NMDARs) in the islets has been proposed to prevent the progress of type 2 diabetes through improving β-cell function. It suggests that a sustained activation of the NMDARs may exhibit deleterious effect on β-cells...
September 4, 2017: Endocrinology
https://www.readbyqxmd.com/read/28936199/bone-status-in-a-patient-with-insulin-like-growth-factor-1-receptor-deletion-syndrome-bone-quality-and-structure-evaluation-using-dual-energy-x-ray-absorptiometry-peripheral-quantitative-computed-tomography-and-quantitative-ultrasonography
#8
Paola Pelosi, Elisabetta Lapi, Loredana Cavalli, Alberto Verrotti, Marilena Pantaleo, Maurizio de Martino, Stefano Stagi
Haploinsufficiency of the insulin-like growth factor (IGF)-1 receptor (IGF1R) gene is a rare, probably under-diagnosed, cause of short stature. However, the effects of IGF1R haploinsufficiency on glucose metabolism, bone status, and metabolism have rarely been investigated. We report the case of a patient referred to our center at the age of 18 months for short stature, failure to thrive, and Silver-Russell-like phenotype. Genetic analysis did not show hypomethylation of the 11p15.5 region or uniparental disomy of chromosome 7...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28935478/development-and-validation-of-a-cell-based-assay-for-the-detection-of-neutralizing-antibodies-against-recombinant-insulins
#9
Sanjukta Chatterjee, Laxmikant Vashishta, Vinit S Waichale, Vivek G Nayak, Ramakrishnan Melarkode, Charles M Donnelly, Patrick T Vallano, Narendra Chirmule, Nilanjan Sengupta
Recombinant biopharmaceuticals can induce generation of anti-drug antibodies, which could potentially neutralize therapeutic drug activity. In this report, we describe development and validation of a cell-based assay for detection of neutralizing antibodies (Nab) against insulin and insulin analogues. In order to achieve clinically meaningful sensitivity the method used an early signalling event, insulin induced insulin receptor phosphorylation as the endpoint. Percentage insulin receptor phosphorylation in cell lysates was measured using ECL based ELISA...
September 18, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28934747/untangling-longevity-dauer-and-healthspan-in-caenorhabditis-elegans-insulin-igf-1-signalling
#10
Collin Yvès Ewald, Jorge Iván Castillo-Quan, T Keith Blackwell
The groundbreaking discovery that lower levels of insulin/IGF-1 signaling (IIS) can induce lifespan extension was reported 24 years ago in the nematode Caenorhabditis elegans. In this organism, mutations in the insulin/IGF-1 receptor gene daf-2 or other genes in this pathway can double lifespan. Subsequent work has revealed that reduced IIS (rIIS) extends lifespan across diverse species, possibly including humans. In C. elegans, IIS also regulates development into the diapause state known as dauer, a quiescent larval form that enables C...
September 22, 2017: Gerontology
https://www.readbyqxmd.com/read/28934649/cooperative-stimulation-of-atherogenesis-by-lipopolysaccharide-and%C3%A2-palmitic-acid-rich-high-fat-diet-in-low-density-lipoprotein-receptor-deficient-mice
#11
Zhongyang Lu, Yanchun Li, Colleen W Brinson, Maria F Lopes-Virella, Yan Huang
BACKGROUND AND AIMS: Either lipopolysaccharide (LPS) or high-fat diet (HFD) enriched with saturated fatty acid (SFA) promotes atherosclerosis. In this study, we investigated the effect of LPS in combination with SFA-rich HFD on atherosclerosis and how LPS and SFA interact to stimulate inflammatory response in vascular endothelial cells. METHODS: Low-density lipoprotein receptor-deficient (LDLR(-/-)) mice were fed a low-fat diet (LFD), HFD with low palmitic acid (PA) (LP-HFD), or HFD with high PA (HP-HFD) for 20 weeks...
September 9, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28934637/igf-system-targeted-therapy-therapeutic-opportunities-for-ovarian-cancer
#12
REVIEW
J A L Liefers-Visser, R A M Meijering, A K L Reyners, A G J van der Zee, S de Jong
The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models...
September 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28933969/psychopharmacological-advances-in-eating-disorders
#13
Hubertus Himmerich, Janet Treasure
Anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) are the primary eating disorders (EDs). The only psychopharmacological treatment options for EDs with approval in some countries include fluoxetine for BN and lisdexamfetamine for BED. Given the high comorbidity and genetic correlations with other psychiatric disorders, it seems possible that novel medications for these conditions might also be effective in EDs. Areas Covered: The current scientific literature has increased our understanding of how medication could be beneficial for patients with EDs on a molecular, functional and behavioral level...
September 21, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28933767/hemin-improves-insulin-sensitivity-and-lipid-metabolism-in-cultured-hepatocytes-and-mice-fed-a-high-fat-diet
#14
Yi Luan, Fang Zhang, Yalan Cheng, Jun Liu, Rui Huang, Menghong Yan, Yuangao Wang, Zhishui He, Hejin Lai, Hui Wang, Hao Ying, Feifan Guo, Qiwei Zhai
Hemin is a breakdown product of hemoglobin. It has been reported that the injection of hemin improves lipid metabolism and insulin sensitivity in various genetic models. However, the effect of hemin supplementation in food on lipid metabolism and insulin sensitivity is still unclear, and whether hemin directly affects cellular insulin sensitivity is yet to be elucidated. Here we show that hemin enhances insulin-induced phosphorylation of insulin receptors, Akt, Gsk3β, FoxO1 and cytoplasmic translocation of FoxO1 in cultured primary hepatocytes under insulin-resistant conditions...
July 26, 2017: Nutrients
https://www.readbyqxmd.com/read/28933050/toll-like-receptor-4-signaling-mediates-inflammation-and-tissue-injury-in-diabetic-nephropathy
#15
REVIEW
Giacomo Garibotto, Annalisa Carta, Daniela Picciotto, Francesca Viazzi, Daniela Verzola
Toll-like receptors (TLRs) are a class of receptors of the innate immune system which detect pathogen-associated and danger-associated molecular patterns in order to initiate an inflammatory response. TLR2 and TLR4 downward signaling causes the production of proinflammatory cytokines that can induce insulin resistance and cardiovascular damage in obesity and type 2 diabetes mellitus. In diabetic nephropathy, TLR4, nucleotide-binding oligomerization domain-containing protein 2 (NOD2), and NLRP3 inflammasome are involved in the production and persistence of inflammation...
September 20, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28932920/microrna-30a-inhibits-colorectal-cancer-metastasis-through-down-regulation-of-type-i-insulin-like-growth-factor-receptor
#16
Y C Liu, Y R Park, S L Kim, S T Lee, S W Kim
BACKGROUND: miR-30a expression is down-regulated and regulates tumor suppressors in various cancers. AIM: We investigated the mechanisms underlying the biological role of miR-30a in CRC. METHODS: MicroRNA, mRNA, and protein expression were analyzed by quantitative real-time PCR and Western blot. The migration and invasion abilities of CRC were determined by wound healing assay, and trans-well migration and invasion. A luciferase reporter assay was used to confirm the targets of miR-30a...
September 20, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28929027/the-role-of-polycarbonate-monomer-bisphenol-a-in-insulin-resistance
#17
Milos Pjanic
Bisphenol A (BPA) is a synthetic unit of polycarbonate polymers and epoxy resins, the types of plastics that could be found in essentially every human population and incorporated into almost every aspect of the modern human society. BPA polymers appear in a wide range of products, from liquid storages (plastic bottles, can and glass linings, water pipes and tanks) and food storages (plastics wraps and containers), to medical and dental devices. BPA polymers could be hydrolyzed spontaneously or in a photo- or temperature-catalyzed process, providing widespread environmental distribution and chronic exposure to the BPA monomer in contemporary human populations...
2017: PeerJ
https://www.readbyqxmd.com/read/28928839/analysis-of-resistance-associated-gene-expression-in-docetaxel-resistant-prostate-cancer-cells
#18
Sangchul Lee, Kwangtaek Kim, Jin-Nyoung Ho, Hyunjin Jin, Seok-Soo Byun, Eunsik Lee
Docetaxel-based chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (CRPC). However, a number of patients with metastatic CRPC are refractory to docetaxel or develop docetaxel resistance. The underlying molecular mechanisms of docetaxel resistance remain unclear, which is a significant burden to the management of metastatic prostate cancer. In the present study, the differential gene expression between docetaxel-sensitive (PC3) and docetaxel-resistant (PC3DR2) prostate cancer cells was identified using DNA microarrays, western blot analysis and reverse transcription-quantitative polymerase chain reaction...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928791/wu-mei-wan-reduces-insulin-resistance-via-inhibition-of-nlrp3-inflammasome-activation-in-hepg2-cells
#19
Xueping Yang, Lingli Li, Ke Fang, Ruolan Dong, Jingbin Li, Yan Zhao, Hui Dong, Ping Yi, Zhaoyi Huang, Guang Chen, Fuer Lu
Wu-Mei-Wan (WMW) is a Chinese herbal formula used to treat type 2 diabetes. In this study, we aimed to explore the effects and mechanisms of WMW on insulin resistance in HepG2 cells. HepG2 cells were pretreated with palmitate (0.25 mM) to impair the insulin signaling pathway. Then, they were treated with different doses of WMW-containing medicated serum and stimulated with 100 nM insulin. Results showed that palmitate could reduce the glucose consumption rate in HepG2 cells and impair insulin signaling related to phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), thereby regulating the downstream signaling pathways...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28928405/nanopore-extended-field-effect-transistor-for-selective-single-molecule-biosensing
#20
Ren Ren, Yanjun Zhang, Binoy Paulose Nadappuram, Bernice Akpinar, David Klenerman, Aleksandar P Ivanov, Joshua B Edel, Yuri Korchev
There has been a significant drive to deliver nanotechnological solutions to biosensing, yet there remains an unmet need in the development of biosensors that are affordable, integrated, fast, capable of multiplexed detection, and offer high selectivity for trace analyte detection in biological fluids. Herein, some of these challenges are addressed by designing a new class of nanoscale sensors dubbed nanopore extended field-effect transistor (nexFET) that combine the advantages of nanopore single-molecule sensing, field-effect transistors, and recognition chemistry...
September 19, 2017: Nature Communications
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