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Insulin signaling heart

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https://www.readbyqxmd.com/read/28301953/glucose-variability-aggravates-cardiac-fibrosis-by-altering-akt-signalling-path
#1
Changjiang Ying, Ting Liu, Hongwei Ling, Mingyue Cheng, Xiaoyan Zhou, Shanshan Wang, Yizhen Mao, Lei Chen, Runze Zhang, Wei Li
OBJECTIVE: To study the effect of blood glucose variability on cardiac fibrosis and its mechanism in a model of diabetic cardiomyopathy. METHODS: A total of 45 Sprague Dawley rats were randomly divided into three groups: control, control diabetes mellitus and fluctuated blood glucose groups. Fluctuated blood glucose was induced by daily subcutaneous insulin and intraperitoneal glucose injections at different time points. Blood lipids and glycosylated haemoglobin A1c were assessed...
March 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28266659/sequential-activation-of-different-pathway-networks-in-ischemia-affected-and-non-affected-myocardium-inducing-intrinsic-remote-conditioning-to-prevent-left-ventricular-remodeling
#2
Noemi Pavo, Dominika Lukovic, Katrin Zlabinger, Abelina Zimba, David Lorant, Georg Goliasch, Johannes Winkler, Dietmar Pils, Katharina Auer, Hendrik Jan Ankersmit, Zoltán Giricz, Tamas Baranyai, Márta Sárközy, András Jakab, Rita Garamvölgyi, Maximilian Y Emmert, Simon P Hoerstrup, Derek J Hausenloy, Péter Ferdinandy, Gerald Maurer, Mariann Gyöngyösi
We have analyzed the pathway networks of ischemia-affected and remote myocardial areas after repetitive ischemia/reperfusion (r-I/R) injury without ensuing myocardial infarction (MI) to elaborate a spatial- and chronologic model of cardioprotective gene networks to prevent left ventricular (LV) adverse remodeling. Domestic pigs underwent three cycles of 10/10 min r-I/R by percutaneous intracoronary balloon inflation/deflation in the mid left anterior descending artery, without consecutive MI. Sham interventions (n = 8) served as controls...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28256297/insulin-and-%C3%AE-adrenergic-receptor-signaling-crosstalk-in-heart
#3
REVIEW
Qin Fu, Qingtong Wang, Yang K Xiang
Recent advances show that insulin may affect β adrenergic receptor (βAR) signaling in the heart to modulate cardiac function in clinically relevant states, such as diabetes mellitus (DM) and heart failure (HF). Conversely, activation of βAR regulates cardiac glucose uptake and promotes insulin resistance (IR) in HF. Here, we discuss the recent characterization of the interaction between the cardiac insulin receptor (InsR) and βAR in the myocardium, in which insulin stimulation crosstalks with cardiac βAR via InsR substrate (IRS)-dependent and G-protein receptor kinase 2 (GRK2)-mediated phosphorylation of β2AR...
February 27, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28246105/insulin-resistance-and-normal-thyroid-hormone-levels-prospective-study-and-metabolomic-analysis
#4
Ele Ferrannini, Giorgio Iervasi, Jeff Cobb, Rudina Ndreu, Monica Nannipieri
While hyper/hypothyroidism causes dysglycemia, the relationship between thyroid hormone levels within the normal range and insulin resistance (IR) is unclear. In 940 participants with strictly normal serum concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH)) followed up for 3 years, we measured insulin sensitivity (by the insulin clamp technique) and a panel of 35 circulating metabolites. At baseline, across quartiles of increasing fT3 levels (or fT3/fT4 ratio) there emerged most features of IR (male sex, higher BMI, waist circumference, heart rate, blood pressure, fatty liver index, free fatty acids, and triglycerides levels, reduced insulin-mediated glucose disposal and ß-cell glucose sensitivity)...
February 28, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28242257/exendin-4-inhibits-structural-remodeling-and-improves-ca-2-homeostasis-in-rats-with-heart-failure-via-the-glp-1-receptor-through-the-enos-cgmp-pkg-pathway
#5
Jingjing Chen, Dandan Wang, Fangai Wang, Shaobo Shi, Yuting Chen, Bo Yang, Yanhong Tang, Congxin Huang
The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 is a long-acting analog of GLP-1, which stimulates insulin secretion and is clinically used in the treatment of type 2 diabetes. Previous studies have demonstrated that GLP-1 agonists and analogs serve as cardioprotective factors in various conditions. Disturbances in calcium cycling are characteristic of heart failure (HF); therefore, the aim of this study was to investigate the effect of exendin-4 (a GLP-1 mimetic) on the regulation of calcium handling and to identify the underlying mechanisms in an HF rat model after myocardial infarction (MI)...
February 24, 2017: Peptides
https://www.readbyqxmd.com/read/28240264/overexpressing-the-novel-autocrine-endocrine-adipokine-wisp2-induces-hyperplasia-of-the-heart-white-and-brown-adipose-tissues-and-prevents-insulin-resistance
#6
John R Grünberg, Jenny M Hoffmann, Shahram Hedjazifar, Annika Nerstedt, Lachmi Jenndahl, Johannes Elvin, John Castellot, Lan Wei, Sofia Movérare-Skrtic, Claes Ohlsson, Louise Mannerås Holm, Fredrik Bäckhed, Ismail Syed, Fatima Bosch, Alan Saghatelian, Barbara B Kahn, Ann Hammarstedt, Ulf Smith
WISP2 is a novel adipokine, most highly expressed in the adipose tissue and primarily in undifferentiated mesenchymal cells. As a secreted protein, it is an autocrine/paracrine activator of canonical WNT signaling and, as an intracellular protein, it helps to maintain precursor cells undifferentiated. To examine effects of increased WISP2 in vivo, we generated an aP2-WISP2 transgenic (Tg) mouse. These mice had increased serum levels of WISP2, increased lean body mass and whole body energy expenditure, hyperplastic brown/white adipose tissues and larger hyperplastic hearts...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228474/changes-in-ambient-temperature-elicit-divergent-control-of-metabolic-and-cardiovascular-actions-by-leptin
#7
Jussara M do Carmo, Alexandre A da Silva, Damian G Romero, John E Hall
Interactions of hypothalamic signaling pathways that control body temperature (BT), blood pressure (BP), and energy balance are poorly understood. We investigated whether the chronic BP and metabolic actions of leptin are differentially modulated by changes in ambient temperature (TA ). Mean arterial pressure (MAP), heart rate (HR), BT, motor activity (MA), and oxygen consumption (Vo2) were measured 24 h/d at normal laboratory TA (23°C), at thermoneutral zone (TNZ, 30°C) for mice or during cold exposure (15°C) in male wild-type mice...
February 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28214558/small-heterodimer-partner-shp-contributes-to-insulin-resistance-in-cardiomyocytes
#8
Ricardo Rodríguez-Calvo, Dipanjan Chanda, Yvonne Oligschlaeger, Marie Miglianico, Will A Coumans, Emma Barroso, Marta Tajes, Joost Jfp Luiken, Jan Fc Glatz, Manuel Vázquez-Carrera, Dietbert Neumann
Small heterodimer partner (SHP) is an atypical nuclear receptor expressed in heart that has been shown to inhibit the hypertrophic response. Here, we assessed the role of SHP in cardiac metabolism and inflammation. Mice fed a high-fat diet (HFD) displayed glucose intolerance accompanied by increased cardiac mRNA levels of Shp. In HL-1 cardiomyocytes, SHP overexpression inhibited both basal and insulin-stimulated glucose uptake and impaired the insulin signalling pathway (evidenced by reduced AKT and AS160 phosphorylation), similar to insulin resistant cells generated by high palmitate/high insulin treatment (HP/HI; 500μM/100nM)...
February 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28209382/err%C3%AE-a-junior-orphan-with-a-senior-role-in-metabolism
#9
REVIEW
Jagannath Misra, Don-Kyu Kim, Hueng-Sik Choi
Estrogen-related receptor (ERR)γ is an orphan nuclear hormone receptor that belongs to the ERR subfamily of transcription factors. No endogenous ligand has been identified to date. ERRγ possesses ligand-independent transcriptional activity that is regulated by co-regulator interactions, and post-translational modifications (PTMs). Recent data from animal models have established ERRγ as a crucial mediator of multiple endocrine and metabolic signals. ERRγ plays important roles in pathological conditions such as insulin resistance, alcoholic liver injury, and cardiac hypertrophy, and controls energy metabolism in the heart, skeletal muscle, and pancreatic β cells...
February 13, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28202772/high-throughput-screening-of-tyrosine-kinase-inhibitor-cardiotoxicity-with-human-induced-pluripotent-stem-cells
#10
Arun Sharma, Paul W Burridge, Wesley L McKeithan, Ricardo Serrano, Praveen Shukla, Nazish Sayed, Jared M Churko, Tomoya Kitani, Haodi Wu, Alexandra Holmström, Elena Matsa, Yuan Zhang, Anusha Kumar, Alice C Fan, Juan C Del Álamo, Sean M Wu, Javid J Moslehi, Mark Mercola, Joseph C Wu
Tyrosine kinase inhibitors (TKIs), despite their efficacy as anticancer therapeutics, are associated with cardiovascular side effects ranging from induced arrhythmias to heart failure. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), generated from 11 healthy individuals and 2 patients receiving cancer treatment, to screen U.S. Food and Drug Administration-approved TKIs for cardiotoxicities by measuring alterations in cardiomyocyte viability, contractility, electrophysiology, calcium handling, and signaling...
February 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28192884/myoinositol-ameliorates-high-fat-diet-and-streptozotocin-induced-diabetes-in-rats-through-promoting-insulin-receptor-signaling
#11
Poovathumkal James Antony, Gopalsamy Rajiv Gandhi, Antony Stalin, Kedike Balakrishna, Erenius Toppo, Kuppusamy Sivasankaran, Savarimuthu Ignacimuthu, Naif Abdullah Al-Dhabi
Mimosa pudica Linn. (Mimosaceae) has been traditionally used for the management of type 2 diabetes mellitus (T2DM) in India. The present study evaluates the therapeutic efficacy of myoinositol (25 and 50mg/kg) isolated from M. pudica stem methanol extract in Triton WR-1339 induced hyperlipidemic and high-fat diet (HFD) fed-streptozotocin (STZ)-induced insulin-resistant diabetic rats. Lipid biomarkers, fasting blood glucose (FBG), changes in body weight, food and water intakes, plasma insulin, HOMA-IR, oral glucose tolerance, intraperitoneal insulin tolerance, urea, creatinine, marker enzymes of liver function, β-cell function and the expression levels of insulin receptor-induced signaling molecules were studied...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28183786/extracellular-rnas-are-associated-with-insulin-resistance-and-metabolic-phenotypes
#12
Ravi Shah, Venkatesh Murthy, Michael Pacold, Kirsty Danielson, Kahraman Tanriverdi, Martin G Larson, Kristina Hanspers, Alexander Pico, Eric Mick, Jared Reis, Sarah de Ferranti, Elizaveta Freinkman, Daniel Levy, Udo Hoffmann, Stavroula Osganian, Saumya Das, Jane E Freedman
OBJECTIVE: Insulin resistance (IR) is a hallmark of obesity and metabolic disease. Circulating extracellular RNAs (ex-RNAs), stable RNA molecules in plasma, may play a role in IR, though most studies on ex-RNAs in IR are small. We sought to characterize the relationship between ex-RNAs and metabolic phenotypes in a large community-based human cohort. RESEARCH DESIGN AND METHODS: We measured circulating plasma ex-RNAs in 2,317 participants without diabetes in the Framingham Heart Study (FHS) Offspring Cohort at cycle 8 and defined associations between ex-RNAs and IR (measured by circulating insulin level)...
February 9, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28179397/dipeptidyl-peptidase-4-induces-aortic-valve-calcification-by-inhibiting-insulin-like-growth-factor-1-signaling-in-valvular-interstitial-cells
#13
Bongkun Choi, Sahmin Lee, Sang-Min Kim, Eun-Jin Lee, Sun Ro Lee, Dae-Hee Kim, Jeong Yoon Jang, Sang-Wook Kang, Ki-Up Lee, Eun-Ju Chang, Jae-Kwan Song
Background -Calcification of the aortic valve leads to increased leaflet stiffness, and consequently to the development of calcific aortic valve disease (CAVD); however, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified that dipeptidyl peptidase-4 (DPP-4, also known as CD26) increases valvular calcification and promotes CAVD progression. Methods -We obtained the aortic valve tissues from humans and murine models (wild type and eNOS(-/-) mice), and cultured the valvular interstitial cells (VICs) and valvular endothelial cells (VECs) from the cusps...
February 8, 2017: Circulation
https://www.readbyqxmd.com/read/28137218/metabolic-and-cardiovascular-actions-of-nesfatin-1-implications-in-health-and-disease
#14
Naresh Ramesh, Kavishankar Gawli, Venkatakiran Pasupulleti, Suraj Unniappan
BACKGROUND: Metabolic homeostasis is achieved by proper functioning of a complex endocrine milieu, comprising of signals arising from the brain and peripheral tissues. Our knowledge of the factors regulating such balance is rapidly evolving, as new signaling molecules are characterized. Of central interest is nesfatin-1, owing to its multifunctional tissue specific actions regulating food intake, body weight, blood glucose and cardiac functions. METHOD: This review discusses the tissue/system wide distribution and actions of nesfatin-1 in regulating metabolic and cardiovascular functions in healthy conditions and diseases...
January 30, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28135006/contribution-of-maladaptive-adipose-tissue-expansion-to-development-of-cardiovascular-disease
#15
Guanghong Jia, Yan Jia, James R Sowers
The overweight and obesity epidemic has led to an increase in the metabolic syndrome and associated cardiovascular disease (CVD). These abnormalities include insulin resistance, type 2 diabetes mellitus, vascular stiffness, hypertension, stroke, and coronary heart disease. Visceral white adipocyte tissue (WAT) expansion and associated fibrosis/stiffness of WAT promote insulin resistance and CVD through increases in proinflammatory adipokines, oxidative stress, activation of renin-angiotensin-aldosterone system, dysregulation of adipocyte apoptosis and autophagy, dysfunctional immune modulation, and adverse changes in the gut microbiome...
December 6, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/28123501/identification-of-the-molecular-mechanisms-underlying-dilated-cardiomyopathy-via-bioinformatic-analysis-of-gene-expression-profiles
#16
Hu Zhang, Zhuo Yu, Jianchao He, Baotong Hua, Guiming Zhang
In the present study, gene expression profiles of patients with dilated cardiomyopathy (DCM) were re-analyzed with bioinformatics tools to investigate the molecular mechanisms underlying DCM. Gene expression dataset GSE3585 was downloaded from Gene Expression Omnibus, which included seven heart biopsy samples obtained from patients with DCM and five healthy controls. Differential analysis was performed using a Limma package in R to screen for differentially expressed genes (DEGs). Functional enrichment analysis was subsequently conducted for DEGs using the Database for Annotation, Visualization and Integration Discovery...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28123046/pde5-inhibitor-tadalafil-and-hydroxychloroquine-co-treatment-provides-synergistic-protection-against-type-2-diabetes-and-myocardial-infarction-in-mice
#17
Rui Wang, Lei Xi, Rakesh C Kukreja
Diabetes is associated with high risk of ischemic heart disease. We previously showed that phosphodiesterase 5 inhibitor - tadalafil (TAD) induces cardioprotection against ischemia/ reperfusion (I/R) injury in diabetic mice. Hydroxychloroquine (HCQ) is a widely used antimalarial and anti-inflammatory drug, which was reported to reduce hyperglycemia in diabetic patients. Therefore we hypothesized that combination of TAD and HCQ may induce synergistic cardioprotection in diabetes. We also investigated the role of insulin-Akt-mTOR signaling, which regulates protein synthesis and cell survival...
January 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28109123/sodium-butyrate-protects-against-high-fat-diet-induced-cardiac-dysfunction-and-metabolic-disorders-in-type-ii-diabetic-mice
#18
Ling Zhang, Jianfeng Du, Naohiro Yano, Hao Wang, Yu Tina Zhao, Dubielecka-Szczerba Patricia, Shougang Zhuang, Eugene Y Chin, Gangjian Qin, Ting C Zhao
Histone deacetylases are recently identified to act as key regulators for cardiac pathophysiology and metabolic disorders. However, the function of histone deacetylase (HDAC) in controlling cardiac performance in type II diabetes and obesity remains unknown. Here we determine whether HDAC inhibition attenuates high fat diet (HFD)-induced cardiac dysfunction and improves metabolic features. Adult mice were fed with either HFD or standard chow food for 24 weeks. Starting at 12 weeks, mice were divided into four groups randomly, in which sodium butyrate (1%), a potent HDAC inhibitor, was provided to chow and HFD-fed mice in drinking water, respectively...
January 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28107204/non-invasive-blood-glucose-detection-system-based-on-conservation-of-energy-method
#19
Yang Zhang, Jian-Ming Zhu, Yong-Bo Liang, Hong-Bo Chen, Shi-Min Yin, Zhen-Cheng Chen
The most common method used for minimizing the occurrence of diabetes complications is frequent glucose testing to adjust the insulin dose. However, using blood glucose (BG) meters presents a risk of infection. It is of great importance to develop non-invasive BG detection techniques. To realize high-accuracy, low-cost and continuous glucose monitoring, we have developed a non-invasive BG detection system using a mixed signal processor 430 (MSP430) microcontroller. This method is based on the combination of the conservation-of-energy method with a sensor integration module, which collects physiological parameters, such as the blood oxygen saturation (SPO2), blood flow velocity and heart rate...
January 20, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28096202/hasf-c3orf58-is-a-novel-ligand-of-the-insulin-like-growth-factor-1-receptor
#20
Akshay Bareja, Conrad Hodgkinson, Alan Payne, Richard Pratt, Victor Dzau
We have recently shown that Hypoxia and Akt induced Stem cell Factor (HASF) protects the heart from ischemia-induced damage and promotes cardiomyocyte proliferation. While we have identified certain signaling pathways responsible for these protective effects, the receptor mediating these effects was unknown. Here, we undertook studies to identify the HASF receptor. A yeast two-hybrid screen identified a partial fragment of Insulin-like Growth Factor 1 Receptor (IGF1R) as a binding partner of HASF. Subsequent co-immunoprecipitation experiments showed that HASF bound to full-length IGF1R...
January 17, 2017: Biochemical Journal
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