Read by QxMD icon Read

insulin receptor

Shlomo Sasson
Activated peroxisome proliferator-activated receptor-δ (PPARδ) induces the expression of genes encoding enzymes that metabolize fatty acids and carbohydrate. Attempts to identify cellular activators of PPARδ produced large lists of various fatty acids and their metabolic derivatives; however, there is no consensus on specific and selective binding interactions of natural ligands with PPARδ. Most models on binding interactions within the ligand binding domain (LBD) of PPARδ have been derived from analyses of PPARδ-LBD crystals formed with synthetic low molecular weight ligands...
October 18, 2016: Biochimie
Katherine R Tuttle, T Dwight McKinney, Jaime A Davidson, Greg Anglin, Kristine D Harper, Fady T Botros
Dulaglutide (DU) is a once-weekly glucagon-like peptide-1 receptor agonist approved for treatment of type 2 diabetes. Integrated data from 9 phase 2 and 3 trials in type 2 diabetes (N = 6005) were used to evaluate effects of DU on estimated glomerular filtration rate (eGFR, mL/min/1.73m(2) [Chronic Kidney Disease Epidemiology Collaboration]), urine albumin-to-creatinine ratio (UACR, mg/g), and kidney adverse events. No significant differences in eGFR were observed during treatment for DU versus placebo (PL), active comparators (AC), or insulin glargine (IG) (mean±SD; DU: 87...
October 21, 2016: Diabetes, Obesity & Metabolism
C Tsentidis, D Gourgiotis, L Kossiva, A Marmarinos, A Doulgeraki, K Karavanaki
: Higher levels of Dickkopf-1, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, could be indicative of downregulated Wnt system, with possible lower osteoblast activation and higher osteoclast signaling in type 1 diabetes mellitus children and adolescents. Dickkopf-1 could significantly contribute to diabetes osteopathy. INTRODUCTION: Increased fracture risk and elevated Dickkopf-1 levels, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, have been documented in adult patients with type 2 diabetes mellitus (T2D), while no relevant data exist on childhood type 1 diabetes (T1D)...
October 20, 2016: Osteoporosis International
Isabel Huang-Doran, Patsy Tomlinson, Felicity Payne, Alexandra Gast, Alison Sleigh, William Bottomley, Julie Harris, Allan Daly, Nuno Rocha, Simon Rudge, Jonathan Clark, Albert Kwok, Stefano Romeo, Emma McCann, Barbara Müksch, Mehul Dattani, Stefano Zucchini, Michael Wakelam, Lazaros C Foukas, David B Savage, Rinki Murphy, Stephen O'Rahilly, Inês Barroso, Robert K Semple
Obesity-related insulin resistance is associated with fatty liver, dyslipidemia, and low plasma adiponectin. Insulin resistance due to insulin receptor (INSR) dysfunction is associated with none of these, but when due to dysfunction of the downstream kinase AKT2 phenocopies obesity-related insulin resistance. We report 5 patients with SHORT syndrome and C-terminal mutations in PIK3R1, encoding the p85α/p55α/p50α subunits of PI3K, which act between INSR and AKT in insulin signaling. Four of 5 patients had extreme insulin resistance without dyslipidemia or hepatic steatosis...
October 20, 2016: JCI Insight
Min Joo Kim, Young Do Koo, Min Kim, Soo Lim, Young Joo Park, Sung Soo Chung, Hak C Jang, Kyong Soo Park
BACKGROUND: Panax ginseng has glucose-lowering effects, some of which are associated with the improvement in insulin resistance in skeletal muscle. Because mitochondria play a pivotal role in the insulin resistance of skeletal muscle, we investigated the effects of the ginsenoside Rg3, one of the active components of P. ginseng, on mitochondrial function and biogenesis in C2C12 myotubes. METHODS: C2C12 myotubes were treated with Rg3 for 24 hours. Insulin signaling pathway proteins were examined by Western blot...
October 2016: Diabetes & Metabolism Journal
Yonghui Yu, Xiao Li, Lingying Liu, Jiake Chai, Zhang Haijun, Wanli Chu, Huinan Yin, Li Ma, Hongjie Duan, Mengjing Xiao
Skeletal muscle atrophy is a common clinical feature among patients with severe burns. Previous studies have shown that miRNAs play critical roles in the regulation of stress-induced skeletal muscle atrophy. Our previous study showed that burn-induced skeletal muscle atrophy is mediated by miR-628. In this study, compared with sham rats, rats subjected to burn injury exhibited skeletal muscle atrophy, as well as significantly decreased insulin receptor substrate 1 (IRS1) protein expression and significantly increased skeletal muscle cell apoptosis...
2016: International Journal of Biological Sciences
Kwong-Fai Wong, Angela M Liu, Wanjin Hong, Zhi Xu, John M Luk
The Hippo pathway regulates the down-stream target Yes-associated protein (YAP) to maintain organ homeostasis, which is commonly inactivated in many types of cancers. However, how cell adhesion dysregulates the Hippo pathway activating YAP oncogene in hepatocellular carcinoma (HCC) remains unclear. Our findings demonstrate that α2β1 integrin (but not other β1 integrins) expressed in HCC cells, after binding to collagen extracellular matrix, could inhibit MST1 kinase phosphorylation and activate YAP pro-oncogenic activities...
October 19, 2016: Oncotarget
Mariya Markova, Olga Pivovarova, Silke Hornemann, Stephanie Sucher, Turid Frahnow, Katrin Wegner, Jürgen Machann, Klaus Jürgen Petzke, Johannes Hierholzer, Ralf Lichtinghagen, Christian Herder, Maren Carstensen-Kirberg, Michael Roden, Natalia Rudovich, Susanne Klaus, Ralph Thomann, Rosemarie Schneeweiss, Sascha Rohn, Andreas F H Pfeiffer
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of hepatic, cardiovascular, and metabolic diseases. High-protein diets, rich in methionine and branched chain amino acids (BCAAs), apparently reduce liver fat but may induce insulin resistance. We investigated the effects of diets high in animal protein vs plant protein, which differ in levels of methionine and BCAA, in subjects with type 2 diabetes and NAFLD. We examined levels of liver fat, lipogenic indices, markers of inflammation, serum levels of fibroblast growth factor 21 (FGF21), and activation of signaling pathways in adipose tissue...
October 17, 2016: Gastroenterology
Susan M Farabaugh, Bonita T Chan, Xiaojiang Cui, Robert K Dearth, Adrian V Lee
BACKGROUND: ErbB2 Receptor Tyrosine Kinase 2 (ErbB2, HER2/Neu) is amplified in breast cancer and associated with poor prognosis. Growing evidence suggests interplay between ErbB2 and insulin-like growth factor (IGF) signaling. For example, ErbB2 inhibitors can block IGF-induced signaling while, conversely, IGF1R inhibitors can inhibit ErbB2 action. ErbB receptors can bind and phosphorylate insulin receptor substrates (IRS) and this may be critical for ErbB-mediated anti-estrogen resistance in breast cancer...
October 21, 2016: Cell Communication and Signaling: CCS
Marc A Becker, Xiaonan Hou, Piyawan Tienchaianada, Brian B Haines, Sean C Harrington, S John Weroha, Sriram Sathyanarayanan, Paul Haluska
BACKGROUND: Mammalian target of rapamycin (mTOR) represents a key downstream intermediate for a myriad of oncogenic receptor tyrosine kinases. In the case of the insulin-like growth factor (IGF) pathway, the mTOR complex (mTORC1) mediates IGF-1 receptor (IGF-1R)-induced estrogen receptor alpha (ERα) phosphorylation/activation and leads to increased proliferation and growth in breast cancer cells. As a result, the prevalence of mTOR inhibitors combined with hormonal therapy has increased in recent years...
October 20, 2016: BMC Cancer
D Bogdanou, M Penna-Martinez, N Filmann, T L Chung, Y Moran-Auth, J Wehrle, C Cappel, S Huenecke, E Herrmann, U Koehl, K Badenhoop
BACKGROUND: Type 1 diabetes mellitus (T1D) is mediated by autoaggressive T effector cells with an underlying regulatory T cell (Treg) defect. Vitamin D (VD) deficiency is highly prevalent in T1D which can aggravate immune dysfunction. High dose VD treatment may enhance Tregs and improve metabolism in T1D patients. METHODS: In a randomized, double-blind, placebo-controlled trial with cross-over design, patients received either for three months cholecalciferol 4000 IU/d, followed by three months placebo or the sequential alternative...
October 20, 2016: Diabetes/metabolism Research and Reviews
Zhu Zeng, Rui Yu, Fanglei Zuo, Bo Zhang, Deju Peng, Huiqin Ma, Shangwu Chen
Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, is an excellent therapeutic peptide drug for type 2 diabetes due to longer lasting biological activity compared to GLP-1. This study explored the feasibility of using probiotic Lactobacillus paracasei as an oral vector for recombinant exendin-4 peptide delivery, an alternative to costly chemical synthesis and inconvenient administration by injection. L. paracasei transformed with a plasmid encoding the exendin-4 gene (L. paracasei L14/pMG76e-exendin-4) with a constitutive promotor was successfully constructed and showed efficient secretion of exendin-4...
2016: PloS One
Kenji Sugawara, Kohei Honda, Yoshie Reien, Norihide Yokoi, Chihiro Seki, Harumi Takahashi, Kohtaro Minami, Ichiro Mori, Akio Matsumoto, Haruaki Nakaya, Susumu Seino
Insulin secretagogues are used for treatment of type 2 diabetes. We attempted to discover novel small molecules to stimulate insulin secretion by using in silico similarity search using sulfonylureas as query, followed by measurement of insulin secretion. Among 38 compounds selected by in silico similarity search, we found three diphenylsemicarbazides and one quinolone that stimulate insulin secretion. We focused on compound 8 (C8), which had the strongest insulin-secreting effect. Based on the structure-activity relationship of C8-derivatives, we identified diphenylthiosemicarbazide (DSC) 108 as the most potent secretagogue...
2016: PloS One
Rüdiger Hardeland
Dynamic aspects of melatonin's actions merit increasing future attention. This concerns particularly entirely different effects in senescent, weakened oscillators and in dysregulated oscillators of cancer cells that may be epigenetically blocked. This is especially obvious in the case of sirtuin 1 (SIRT1) which is upregulated by melatonin in aged tissues, but strongly downregulated in several cancer cells. These findings are not at all controversial, but are explained on the basis of divergent changes in weakened and dysregulated oscillators...
October 20, 2016: Journal of Pineal Research
Fabio Broglio, Edoardo Mannucci, Raffaele Napoli, Antonio Nicolucci, Francesco Purrello, Elena Nikonova, William Stager, Roberto Trevisan
AIMS: To evaluate long term efficacy and safety of lixisenatide, a short-acting, prandial GLP-1 RA (Glucagon-Like Peptide-1 Receptor Agonists) as add-on therapy in type 2 diabetes mellitus. METHODS: A meta-analysis of 76-week results of five placebo-controlled clinical trials from the GetGoal program was performed including 3,000 inadequately controlled adult diabetic patients where lixisenatide 20 µg once-daily was administered in combination with metformin (GetGoal-M and GetGoal-F1), sulphonylurea ± metformin (GetGoal-S), basal insulin ± metformin (GetGoal-L) or pioglitazone ± metformin (GetGoal-P)...
October 20, 2016: Diabetes, Obesity & Metabolism
Attilio Pingitore, Edward S Chambers, Thomas Hill, Inmaculada Ruz Maldonado, Bo Liu, Gavin Bewick, Douglas J Morrison, Tom Preston, Gareth A Wallis, Catriona Tedford, Ramón Castañera González, Guo Cai Huang, Pratik Choudhary, Gary Frost, Shanta J Persaud
AIMS: Diet-derived short chain fatty acids (SCFAs) improve glucose homeostasis in vivo, but the role of individual SCFAs and their mechanisms of action have not been defined. This study evaluated the effects of increasing colonic delivery of the SCFA propionate on β-cell function in humans and the direct effects of propionate on isolated human islets in vitro. MATERIALS AND METHODS: For 24 weeks human subjects ingested an inulin-propionate ester that delivers propionate to the colon...
October 20, 2016: Diabetes, Obesity & Metabolism
John A Karas, Nitin A Patil, Julien Tailhades, Marc-Antoine Sani, Denis B Scanlon, Briony E Forbes, James Gardiner, Frances Separovic, John D Wade, Mohammed Akhter Hossain
Despite recent advances in the treatment of diabetes mellitus, storage of insulin formulations at 4 °C is still necessary to minimize chemical degradation. This is problematic in tropical regions where reliable refrigeration is not ubiquitous. Some degradation byproducts are caused by disulfide shuffling of cystine that leads to covalently bonded oligomers. Consequently we examined the utility of the non-reducible cystine isostere, cystathionine, within the A-chain. Reported herein is an efficient method for forming this mimic using simple monomeric building blocks...
October 20, 2016: Angewandte Chemie
FangFang, Hongyan Li, Tingting Qin, Min Li, Shiping Ma
The impaired insulin signaling has been recognized as a common pathogenetic mechanism between diabetes and Alzheimer's disease (AD). In the progression of AD, brain is characterized by defective insulin receptor substrate-1 (IRS-1) and increased oxidative stress. Thymol, a monoterpene phenol isolated from medicinal herbs, has exhibited robust neuroprotective effects. The present study was designed to investigate the protective effect of thymol on HFD-induced cognitive deficits, and explore the possible mechanisms...
October 20, 2016: Metabolic Brain Disease
Ana C Puhl, Paul Webb, Igor Polikarpov
Loss-of-function mutation V290M in the ligand-binding domain of the peroxisome proliferator activated receptor γ (PPARγ) is associated with a ligand resistance syndrome (PLRS), characterized by partial lipodystrophy and severe insulin resistance. In this data article we discuss an X-ray diffraction dataset that yielded the structure of PPARγ LBD V290M mutant refined at 2.3 Å resolution, that allowed building of 3D model of the receptor mutant with high confidence and revealed continuous well-defined electron density for the partial agonist diclofenac bound to hydrophobic pocket of the PPARγ...
June 2016: Data in Brief
Yong Xie, Yi Zhang, Zebin Guo, Hongliang Zeng, Baodong Zheng
This study aimed to investigate the effects of total alkaloids from Nelumbinis Plumula (NPA) on insulin resistance (IR) of high-fat diet- (HFD-) induced nonalcoholic fatty liver disease (NAFLD). Rats were fed with HFD for 8 weeks to induce NAFLD. Then, the effect of NPA on ameliorating IR in HFD-induced NAFLD was evaluated. Fasting serum insulin was determined using an enzyme-linked immunosorbent assay (ELISA) kit for insulin following the manufacturer's protocol. Some inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were determined using ELISA kits to assess the inflammatory burden in rats...
2016: Journal of Diabetes Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"