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Cardiac insulin signaling

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https://www.readbyqxmd.com/read/29217479/distinct-lipidomic-profiles-in-models-of-physiological-and-pathological-cardiac-remodeling-and-potential-therapeutic-strategies
#1
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
#2
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/29185069/connexin-43-and-atp-sensitive-potassium-channels-crosstalk-a-missing-link-in-hypoxia-ischemia-stress
#3
REVIEW
Ajaz Ahmad Waza, Shabir Ahmad Bhat, Mahboob Ul Hussain, Bashir A Ganai
Connexin 43 (Cx43) is a gap junction protein expressed in various tissues and organs of vertebrates. Besides functioning as a gap junction, Cx43 also regulates diverse cellular processes like cell growth and differentiation, cell migration, cell survival, etc. Cx43 is critical for normal cardiac functioning and is therefore abundantly expressed in cardiomyocytes. On the other hand, ATP-sensitive potassium (KATP) channels are metabolic sensors converting metabolic changes into electrical activity. These channels are important in maintaining the neurotransmitter release, smooth muscle relaxation, cardiac action potential repolarization, normal physiology of cellular repolarization, insulin secretion and immune function...
November 29, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29180262/inhibition-of-hsf2-sumoylation-via-mel18-upregulates-igf-iir-and-leads-to-hypertension-induced-cardiac-hypertrophy
#4
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
#5
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...
November 23, 2017: 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
#6
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
#7
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
#8
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/29136335/sii-ang-ii-potentiates-insulin-receptor-signalling-and-glycogen-synthesis-in-hepatocytes
#9
Samra Joke Sanni, Christina Lyngsø, Steen Gammeltoft, Jakob Lerche Hansen
The angiotensin II type I receptor (AT1R) is involved in the regulation of cardiovascular function. Excessive activation of AT1R by angiotensin II (Ang II) leads to cardiovascular disease and may be involved in the development of insulin resistance and diabetes. Functionally selective Ang II analogues, such as the [Sar1, Ile4, Ile8]-angiotensin II (SII Ang II) analogue that only activates a subset of signalling networks have been demonstrated to have beneficial effects on cardiovascular function in certain settings, including lowering blood pressure and increasing cardiac performance...
November 14, 2017: Basic & Clinical Pharmacology & Toxicology
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
#10
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/29109032/molecular-mechanisms-of-cardiac-pathology-in-diabetes-experimental-insights
#11
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/29104486/tanshinone-iia-inhibits-%C3%AE-catenin-nuclear-translocation-and-igf-2r-activation-via-estrogen-receptors-to-suppress-angiotensin-ii-induced-h9c2-cardiomyoblast-cell-apoptosis
#12
Ya-Fang Chen, Cecilia Hsuan Day, Nien-Hung Lee, Yu-Feng Chen, Jaw-Ji Yang, Chih-Hsueh Lin, Ray-Jade Chen, Peramaiyan Rajendran, Vijaya Padma Viswanadha, Chih-Yang Huang
Cardiomyopathy involves changes in the myocardial ultra-structure, hypertrophy, apoptosis, fibrosis and inflammation. Angiotensin II (AngII) stimulates the expression of insulin like-growth factors (IGF-2) and IGF-2 receptor (IGF-2R) in H9c2 cardiomyoblasts and subsequently leads to apoptosis. Estrogen receptors protect cardiomyocytes from apoptosis and fibrosis. Tanshinone IIA (TSN), a main active ingredient from Danshen, has been shown to protect cardiomyocytes from death caused by different stress signals...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29101170/the-prorenin-receptor-in-the-cardiovascular-system-and-beyond
#13
Matthew T Hennrikus, Alexis A Gonzalez, Minolfa C Prieto
Since the prorenin receptor (PRR) was first reported, investigations into its role in many cellular processes have been underway. Renin and prorenin binding to PRR and its soluble form (sPRR) increases angiotensin I formation and intracellular pathways resulting in induction of profibrotic factors. The PRR has supplementary roles as a vital accessory protein of the vacuolar-type H+-ATPase and also as an intermediate in Wnt signaling. As a component of the H-ATPase, the PRR has been found upregulated during cardiac stress...
November 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29098623/the-igf1-pi3k-akt-signaling-pathway-in-mediating-exercise-induced-cardiac-hypertrophy-and-protection
#14
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
#15
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
https://www.readbyqxmd.com/read/29058194/characterization-of-mc4r-regulation-of-the-kir7-1-channel-using-the-tl-flux-assay
#16
Michael J Litt, Roger D Cone, Masoud Ghamari-Langroudi
The family of inward rectifying potassium channels (Kir channels) plays crucial roles in the regulation of heart rhythms, renal excretion, insulin release, and neuronal activity. Their dysfunction has been attributed to numerous diseases such as cardiac arrhythmia, kidney failure and electrolyte imbalance, diabetes mellitus, epilepsy, retinal degeneration, and other neuronal disorders. We have recently demonstrated that the melanocortin-4 receptor (MC4R), a Gαs-coupled GPCR, regulates Kir7.1 activity through a mechanism independent of Gαs and cAMP...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29057227/getting-old-through-the-blood-circulating-molecules-in-aging-and-senescence-of-cardiovascular-regenerative-cells
#17
REVIEW
Francesco Angelini, Francesca Pagano, Antonella Bordin, Vittorio Picchio, Elena De Falco, Isotta Chimenti
Global aging is a hallmark of our century. The natural multifactorial process resulting in aging involves structural and functional changes, affecting molecules, cells, and tissues. As the western population is getting older, we are witnessing an increase in the burden of cardiovascular events, some of which are known to be directly linked to cellular senescence and dysfunction. In this review, we will focus on the description of a few circulating molecules, which have been correlated to life span, aging, and cardiovascular homeostasis...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29052864/short-term-hypoxia-upregulated-mas-receptor-expression-to-repress-the-at1-r-signaling-pathway-and-attenuate-ang-ii-induced-cardiomyocyte-apoptosis
#18
Ruey-Lin Chang, Chih-Fen Chang, Da-Tong Ju, Tsung-Jung Ho, Tung-Ti Chang, Jing-Wei Lin, Jia-Chun Le, Shiu-Min Cheng, Cecilia-Hsuan Day, V Vijaya Padma, Chih-Yang Huang
Hypertension-stimulated cardiac hypertrophy and apoptosis play critical roles in the progression of heart failure. Our previous study suggested that hypertensive angiotensin II (Ang II) enhanced insulin-like growth factor receptor II (IGF-IIR) expression and cardiomyocyte apoptosis, which are involved JNK activation, sirtuin1 (SIRT1) degradation, and heat-shock transcription factor 1 (HSF1) acetylation. Moreover, previous studies have implied that short-term hypoxia (STH) might exert cardioprotective effects...
October 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29043508/the-role-of-pi3k%C3%AE-isoform-in-cardioprotection
#19
Xavier Rossello, Jaime A Riquelme, Zhenhe He, Stasa Taferner, Bart Vanhaesebroeck, Sean M Davidson, Derek M Yellon
Ischemic preconditioning (IPC) limits myocardial infarct size through the activation of the PI3K-Akt signal cascade; however, little is known about the roles of individual PI3K isoforms in cardioprotection. We aimed, therefore, to elucidate the role of the PI3Kα isoform in cardioprotection Pharmacological PI3Kα inhibition was assessed in isolated-perfused mouse hearts subjected to ischemia/reperfusion injury (IRI), either during the IPC procedure or at reperfusion. PI3Kα inhibition abrogated the IPC-induced protective effect at reperfusion, but not when given only during the IPC protocol...
October 17, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29021167/high-density-lipoprotein-delivered-after-myocardial-infarction-increases-cardiac-glucose-uptake-and-function-in-mice
#20
Sarah E Heywood, Adele L Richart, Darren C Henstridge, Karen Alt, Helen Kiriazis, Claire Zammit, Andrew L Carey, Helene L Kammoun, Lea M Delbridge, Medini Reddy, Yi-Ching Chen, Xiao-Jun Du, Christoph E Hagemeyer, Mark A Febbraio, Andrew L Siebel, Bronwyn A Kingwell
Protecting the heart after an acute coronary syndrome is a key therapeutic goal to support cardiac recovery and prevent progression to heart failure. A potential strategy is to target cardiac glucose metabolism at the early stages after ischemia when glycolysis is critical for myocyte survival. Building on our discovery that high-density lipoprotein (HDL) modulates skeletal muscle glucose metabolism, we now demonstrate that a single dose of reconstituted HDL (rHDL) delivered after myocardial ischemia increases cardiac glucose uptake, reduces infarct size, and improves cardiac remodeling in association with enhanced functional recovery in mice...
October 11, 2017: Science Translational Medicine
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