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Insulin signaling heart

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https://www.readbyqxmd.com/read/29341865/evidence-of-genetic-predisposition-for-metabolically-healthy-obesity-and-metabolically-obese-normal-weight
#1
Lam Opal Huang, Ruth Loos, Tuomas Oskari Kilpeläinen
Obesity has evolved into a global pandemic, which constitutes a major threat to public health. The majority of obesity-related health care costs are due to cardiometabolic complications, such as insulin resistance, dyslipidemia, and hypertension, which are risk factors for type 2 diabetes and cardiovascular disease. However, many obese individuals, often called metabolically healthy obese (MHO), seem to be protected from these cardiometabolic complications. Conversely, there is a group of individuals who suffer from cardiometabolic complications despite being of normal weight; a condition termed metabolically obese normal weight (MONW)...
December 20, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29277329/human-embryonic-stem-cell-derived-cardiomyocytes-as-an-in-vitro-model-to-study-cardiac-insulin-resistance
#2
Ilvy M E Geraets, Dipanjan Chanda, Florence H J van Tienen, Arthur van den Wijngaard, Rick Kamps, Dietbert Neumann, Yilin Liu, Jan F C Glatz, Joost J F P Luiken, Miranda Nabben
Patients with type 2 diabetes (T2D) and/or insulin resistance (IR) have an increased risk for the development of heart failure (HF). Evidence indicates that this increased risk is linked to an altered cardiac substrate preference of the insulin resistant heart, which shifts from a balanced utilization of glucose and long-chain fatty acids (FAs) towards an almost complete reliance on FAs as main fuel source. This shift leads to a loss of endosomal proton pump activity and increased cardiac fat accumulation, which eventually triggers cardiac dysfunction...
December 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29247377/ccn5-wisp2-and-metabolic-diseases
#3
REVIEW
John R Grünberg, Johannes Elvin, Alexandra Paul, Shahram Hedjazifar, Ann Hammarstedt, Ulf Smith
Obesity and type 2 diabetes increase worldwide at an epidemic rate. It is expected that by the year 2030 around 500 million people will have diabetes; predominantly type 2 diabetes. The CCN family of proteins has become of interest in both metabolic and other common human diseases because of their effects on mesenchymal stem cell (MSCs) proliferation and differentiation as well as being important regulators of fibrosis. We here review current knowledge of the WNT1 inducible signaling pathway protein 2 (CCN5/WISP2)...
December 15, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29236751/lysophosphatidic-acid-receptor-mrna-levels-in-heart-and-white-adipose-tissue-are-associated-with-obesity-in-mice-and-humans
#4
Amy Brown, Intekhab Hossain, Lester J Perez, Carine Nzirorera, Kathleen Tozer, Kenneth D'Souza, Purvi C Trivedi, Christie Aguiar, Alexandra M Yip, Jennifer Shea, Keith R Brunt, Jean-Francois Legare, Ansar Hassan, Thomas Pulinilkunnil, Petra C Kienesberger
BACKGROUND: Lysophosphatidic acid (LPA) receptor signaling has been implicated in cardiovascular and obesity-related metabolic disease. However, the distribution and regulation of LPA receptors in the myocardium and adipose tissue remain unclear. OBJECTIVES: This study aimed to characterize the mRNA expression of LPA receptors (LPA1-6) in the murine and human myocardium and adipose tissue, and its regulation in response to obesity. METHODS: LPA receptor mRNA levels were determined by qPCR in i) heart ventricles, isolated cardiomyocytes, and perigonadal adipose tissue from chow or high fat-high sucrose (HFHS)-fed male C57BL/6 mice, ii) 3T3-L1 adipocytes and HL-1 cardiomyocytes under conditions mimicking gluco/lipotoxicity, and iii) human atrial and subcutaneous adipose tissue from non-obese, pre-obese, and obese cardiac surgery patients...
2017: PloS One
https://www.readbyqxmd.com/read/29234032/heat-failure-phenotypes-induced-by-knockdown-of-dapit-in-zebrafish-a-new-insight-into-mechanism-of-dilated-cardiomyopathy
#5
Yoji Nagata, Masakazu Yamagishi, Tetsuo Konno, Chiaki Nakanishi, Yoshihiro Asano, Shin Ito, Yuri Nakajima, Osamu Seguchi, Noboru Fujino, Masa-Aki Kawashiri, Seiji Takashima, Masafumi Kitakaze, Kenshi Hayashi
The pathogenesis of heart failure associated with dilated cardiomyopathy (DCM) may result in part from adenosine triphosphate (ATP) dysregulation in the myocardium. Under these conditions, diabetes-associated protein in insulin-sensitive tissue (DAPIT), which is encoded by the upregulated during skeletal muscle growth 5 (USMG5) gene, plays a crucial role in energy production by mitochondrial ATP synthase. To determine whether USMG5 is related to the development of heart failure, we performed clinical and experimental studies...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29228671/metformin-ameliorates-skeletal-muscle-insulin-resistance-by-inhibiting-mir-21-expression-in-a-high-fat-dietary-rat-model
#6
Jinyang Wang, Yanbin Gao, Lijun Duan, Suhong Wei, Jing Liu, Liming Tian, Jinxing Quan, Qi Zhang, Juxiang Liu, Jinkui Yang
Insulin resistance (IR) plays a major role in the pathogenesis of abdominal obesity, hypertension, coronary heart disease, atherosclerosis and diabetes. miR-21 and TGF-β/smads is closely related to IR. However, it remained elusive whether metformin improved skeletal muscle insulin resistance (IRSM) by regulating miR-21 and its target signal TGF-β1/smads expression. In this study, high-fat diet rats with IR model and IR-skeletal muscle L6 cells (L6-SMCs) model were established, insulin sensitive index (ISI) and Homeostasis model assessment of IR (HOMA-IR) were applied, miR-21 and TGF-β1/smads mRNA expression were examined by RT-PCR, smad3 and smad7 protein were detected by western-blotting and laser scanning confocal microscopy (LSCM), the valid target of miR-21 was detected by luciferase reporter gene assay...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217479/distinct-lipidomic-profiles-in-models-of-physiological-and-pathological-cardiac-remodeling-and-potential-therapeutic-strategies
#7
Yow Keat Tham, Kevin Huynh, Natalie A Mellett, Darren C Henstridge, Helen Kiriazis, Jenny Y Y Ooi, Aya Matsumoto, Natalie L Patterson, Junichi Sadoshima, Peter J Meikle, Julie R McMullen
Cardiac myocyte membranes contain lipids which remodel dramatically in response to heart growth and remodeling. Lipid species have both structural and functional roles. Physiological and pathological cardiac remodeling have very distinct phenotypes, and the identification of molecular differences represent avenues for therapeutic interventions. Whether the abundance of specific lipid classes is different in physiological and pathological models was largely unknown. The aim of this study was to determine whether distinct lipids are regulated in settings of physiological and pathological remodeling, and if so, whether modulation of differentially-regulated lipids could modulate heart size and function...
December 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29203581/cardiac-insulin-signaling-regulates-glycolysis-through-phosphofructokinase-2-content-and-activity
#8
Lee B Bockus, Satoshi Matsuzaki, Shraddha S Vadvalkar, Zachary T Young, Jennifer R Giorgione, Maria F Newhardt, Michael Kinter, Kenneth M Humphries
BACKGROUND: The healthy heart has a dynamic capacity to respond and adapt to changes in nutrient availability. Diabetes mellitus disrupts this metabolic flexibility and promotes cardiomyopathy through mechanisms that are not completely understood. Phosphofructokinase 2 (PFK-2) is a primary regulator of cardiac glycolysis and substrate selection, yet its regulation under normal and pathological conditions is unknown. This study was undertaken to determine how changes in insulin signaling affect PFK-2 content, activity, and cardiac metabolism...
December 4, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29180262/inhibition-of-hsf2-sumoylation-via-mel18-upregulates-igf-iir-and-leads-to-hypertension-induced-cardiac-hypertrophy
#9
Chih-Yang Huang, Chia-Hua Kuo, Pei-Ying Pai, Tsung-Jung Ho, Yueh-Min Lin, Ray-Jade Chen, Fuu-Jen Tsai, V Vijaya Padma, Wei-Wen Kuo, Chih-Yang Huang
Cardiac hypertrophy is a major characteristic of early-stage hypertension-related heart failure. We have found that the insulin-like growth factor receptor II (IGF-IIR) signaling was critical for hypertensive angiotensin II-induced cardiomyocyte hypertrophy and apoptosis. Moreover, this IGF-IIR signaling was elegantly modulated by the heat shock transcription factors (HSFs) during heart failure. However, the detailed mechanism by which HSFs regulates IGF-IIR during hypertension-induced cardiac hypertrophy remains elusive...
November 10, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/29166798/grk2-as-a-therapeutic-target-for-heart-failure
#10
Alessandro Cannavo, Klara Komici, Leonardo Bencivenga, Maria Loreta D'amico, Giuseppina Gambino, Daniela Liccardo, Nicola Ferrara, Giuseppe Rengo
G protein-coupled receptor (GPCR) kinase-2 (GRK2) is a regulator of GPCRs, in particular β-adrenergic receptors (ARs), and as demonstrated by decades of investigation, it has a pivotal role in the development and progression of cardiovascular disease, like heart failure (HF). Indeed elevated levels and activity of this kinase are able to promote the dysfunction of both cardiac and adrenal α- and β-ARs and to dysregulate other protective signaling pathway, such as sphingosine 1-phospate and insulin. Moreover, recent discoveries suggest that GRK2 can signal independently from GPCRs, in a 'non-canonical' manner, via interaction with non-GPCR molecule or via its mitochondrial localization...
January 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29163503/efferocytosis-and-outside-in-signaling-by-cardiac-phagocytes-links-to-repair-cellular-programming-and-intercellular-crosstalk-in-heart
#11
REVIEW
Matthew DeBerge, Shuang Zhang, Kristofor Glinton, Luba Grigoryeva, Islam Hussein, Esther Vorovich, Karen Ho, Xunrong Luo, Edward B Thorp
Phagocytic sensing and engulfment of dying cells and extracellular bodies initiate an intracellular signaling cascade within the phagocyte that can polarize cellular function and promote communication with neighboring non-phagocytes. Accumulating evidence links phagocytic signaling in the heart to cardiac development, adult myocardial homeostasis, and the resolution of cardiac inflammation of infectious, ischemic, and aging-associated etiology. Phagocytic clearance in the heart may be carried out by professional phagocytes, such as macrophages, and non-professional cells, including myofibrolasts and potentially epithelial cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29152614/ataxia-telangiectasia-mutated-kinase-role-in-myocardial-remodeling
#12
Patsy Thrasher, Mahipal Singh, Krishna Singh
Ataxia-telangiectasia mutated kinase (ATM) is a serine/threonine kinase. Mutations in the ATM gene cause a rare autosomal multisystemic disease known as Ataxia-telangiectasia (AT). Individuals with mutations in both copies of the ATM gene suffer from increased susceptibility to ionizing radiation, predisposition to cancer, insulin resistance, immune deficiency, and premature aging. Patients with one mutated allele make-up ~1.4 to 2% of the general population. These individuals are spared from most of the symptoms of the disease...
2017: Journal of Rare Diseases Research & Treatment
https://www.readbyqxmd.com/read/29136764/cardiac-apoptosis-induced-under-high-glucose-condition-involves-activation-of-igf2r-signaling-in-h9c2-cardiomyoblasts-and-streptozotocin-induced-diabetic-rat-hearts
#13
Chih-Chung Feng, Sudhir Pandey, Ching-Yuang Lin, Chia-Yao Shen, Ruey-Lin Chang, Tung-Ti Chang, Ray-Jade Chen, Vijaya Padma Viswanadha, Yueh-Min Lin, Chih-Yang Huang
The insulin-like growth factor type 2 receptor (IGF2R) overexpression has been implicated in heart disease progression. Unregulated IGF2R signaling triggers cardiac hypertrophy, apoptosis, and cardiomyopathies. The present study investigated the role of IGF2R in cardiomyocyte apoptosis under high glucose (HG) levels and in streptozotocin (STZ) induced diabetic rat hearts. We found that IGF2 and IGF2R protein expression were highly upregulated under high glucose condition in H9c2 cells as well as in STZ induced diabetic rat hearts...
November 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29115461/histone-deacetylase-inhibition-of-cardiac-autophagy-in-rats-on-a-high%C3%A2-fat-diet-with-low%C3%A2-dose-streptozotocin-induced-type-2-diabetes-mellitus
#14
Ting-I Lee, Kuan-Jen Bai, Yao-Chang Chen, Ting-Wei Lee, Cheng-Chih Chung, Wen-Chih Tsai, Shin-Yi Tsao, Yu-Hsun Kao
Autophagy serves a role in preserving cellular homeostasis. Diabetes mellitus (DM) impairs cardiac autophagy and is associated with an accumulation of cytotoxic proteins that may provoke apoptosis and damage cardiomyocytes. Histone deacetylase (HDAC) inhibitors attenuate cardiac fibrosis and inflammation, and improve cardiomyopathy resulting from DM. However, the effect of HDAC inhibition on autophagy in DM cardiomyopathy has not been investigated. The purpose of the present study was to evaluate whether HDAC inhibition modulates cardiac autophagy and to investigate the potential mechanisms in type 2 DM (T2DM) hearts...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115400/global-gene-expression-analysis-combined-with-a-genomics-approach-for-the-identification-of-signal-transduction-networks-involved-in-postnatal-mouse-myocardial-proliferation-and-development
#15
Ruoxin Wang, Chao Su, Xinting Wang, Qiang Fu, Xingjie Gao, Chunyan Zhang, Jie Yang, Xi Yang, Minxin Wei
Mammalian cardiomyocytes may permanently lose their ability to proliferate after birth. Therefore, studying the proliferation and growth arrest of cardiomyocytes during the postnatal period may enhance the current understanding regarding this molecular mechanism. The present study identified the differentially expressed genes in hearts obtained from 24 h‑old mice, which contain proliferative cardiomyocytes; 7‑day‑old mice, in which the cardiomyocytes are undergoing a proliferative burst; and 10‑week‑old mice, which contain growth‑arrested cardiomyocytes, using global gene expression analysis...
November 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29109913/comparative-analysis-of-the-microrna-transcriptome-between-yak-and-cattle-provides-insight-into-high-altitude-adaptation
#16
Jiuqiang Guan, Keren Long, Jideng Ma, Jinwei Zhang, Dafang He, Long Jin, Qianzi Tang, Anan Jiang, Xun Wang, Yaodong Hu, Shilin Tian, Zhi Jiang, Mingzhou Li, Xiaolin Luo
Extensive and in-depth investigations of high-altitude adaptation have been carried out at the level of morphology, anatomy, physiology and genomics, but few investigations focused on the roles of microRNA (miRNA) in high-altitude adaptation. We examined the differences in the miRNA transcriptomes of two representative hypoxia-sensitive tissues (heart and lung) between yak and cattle, two closely related species that live in high and low altitudes, respectively. In this study, we identified a total of 808 mature miRNAs, which corresponded to 715 pre-miRNAs in the two species...
2017: PeerJ
https://www.readbyqxmd.com/read/29109032/molecular-mechanisms-of-cardiac-pathology-in-diabetes-experimental-insights
#17
REVIEW
U Varma, P Koutsifeli, V L Benson, K M Mellor, L M D Delbridge
Diabetic cardiomyopathy is a distinct pathology independent of co-morbidities such as coronary artery disease and hypertension. Diminished glucose uptake due to impaired insulin signaling and decreased expression of glucose transporters is associated with a shift towards increased reliance on fatty acid oxidation and reduced cardiac efficiency in diabetic hearts. The cardiac metabolic profile in diabetes is influenced by disturbances in circulating glucose, insulin and fatty acids, and alterations in cardiomyocyte signaling...
November 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29098797/acylated-ghrelin-treatment-normalizes-skeletal-muscle-mitochondrial-oxidative-capacity-and-akt-phosphorylation-in-rat-chronic-heart-failure
#18
Rocco Barazzoni, Gianluca Gortan Cappellari, Sandra Palus, Pierandrea Vinci, Giulia Ruozi, Michela Zanetti, Annamaria Semolic, Nicole Ebner, Stephan von Haehling, Gianfranco Sinagra, Mauro Giacca, Jochen Springer
BACKGROUND: Chronic heart failure (CHF) is associated with skeletal muscle abnormalities contributing to exercise intolerance, muscle loss, and negative impact on patient prognosis. A primary role has been proposed for mitochondrial dysfunction, which may be induced by systemic and tissue inflammation and further contribute to low insulin signalling. The acylated form of the gastric hormone ghrelin (AG) may improve mitochondrial oxidative capacity and insulin signalling in both healthy and diseased rodent models...
December 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29098623/the-igf1-pi3k-akt-signaling-pathway-in-mediating-exercise-induced-cardiac-hypertrophy-and-protection
#19
Kate L Weeks, Bianca C Bernardo, Jenny Y Y Ooi, Natalie L Patterson, Julie R McMullen
Regular physical activity or exercise training can lead to heart enlargement known as cardiac hypertrophy. Cardiac hypertrophy is broadly defined as an increase in heart mass. In adults, cardiac hypertrophy is often considered a poor prognostic sign because it often progresses to heart failure. Heart enlargement in a setting of cardiac disease is referred to as pathological cardiac hypertrophy and is typically characterized by cell death and depressed cardiac function. By contrast, physiological cardiac hypertrophy, as occurs in response to chronic exercise training (i...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29079702/metallothionein-preserves-akt2-activity-and-cardiac-function-via-inhibiting-trb3-in-diabetic-hearts
#20
Junlian Gu, Xiaoqing Yan, Xiaozhen Dai, Yuehui Wang, Qian Lin, Jian Xiao, Shanshan Zhou, Jian Zhang, Kai Wang, Jun Zeng, Ying Xin, Michelle T Barati, Chi Zhang, Yang Bai, Yan Li, Paul N Epstein, Kupper A Wintergerst, Xiaokun Li, Yi Tan, Lu Cai
Cardiac insulin resistance is a key pathogenic factor for diabetic cardiomyopathy (DCM), but the mechanism remains largely unclear. We found that diabetic hearts exhibited decreased phosphorylation of total Akt and isoform Akt2 but not Akt1 in wild type (WT) male FVB mice, which was accompanied by attenuation of Akt downstream glucose metabolic signal; All these signal changes were not observed in metallothionein cardiac-specific transgenic (MT-TG) hearts. Furthermore, insulin-induced glucose metabolic signals were attenuated only in WT diabetic hearts...
October 27, 2017: Diabetes
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