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Cardiac insulin signaling

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https://www.readbyqxmd.com/read/29043508/the-role-of-pi3k%C3%AE-isoform-in-cardioprotection
#1
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
#2
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
https://www.readbyqxmd.com/read/29017896/mg53-and-disordered-metabolism-in-striated-muscle
#3
REVIEW
Xinli Hu, Rui-Ping Xiao
MG53 is a member of tripartite motif family (TRIM) that expressed most abundantly in striated muscle. Using rodent models, many studies have demonstrated the MG53 not only facilitates membrane repair after ischemia reperfusion injury, but also contributes to the protective effects of both pre- and post-conditioning. Recently, however, it has been shown that MG53 participates in the regulation of many metabolic processes, especially insulin signaling pathway. Thus, sustained overexpression of MG53 may contribute to the development of various metabolic disorders in striated muscle...
October 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28989026/activation-of-nuclear-%C3%AE-catenin-c-myc-axis-promotes-oxidative-stress-injury-in-streptozotocin-induced-diabetic-cardiomyopathy
#4
Peng Liu, Jianfang Su, Xixi Song, Shixiao Wang
Myocardial oxidative stress injury plays a crucial role in the pathogenesis of diabetic cardiomyopathy (DCM). Wnt/β-catenin signaling has been reported to involve in various heart diseases. However, the underlying mechanism associated with β-catenin in DCM remains elusive. This study intended to explore the effect of β-catenin on oxidative damage of DCM by establishing streptozotocin (STZ)-induced diabetic mouse model and hydrogen peroxide (H2O2)-treated myocardial cell model. Cardiac oxidative stress in DCM was detected by measurements of lipid peroxidation and anti-oxidative enzyme activities as well as DHE staining...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28967097/chronic-treatment-with-novel-nanoformulated-micelles-of-rapamycin-rapatar-protects-diabetic-heart-against-ischemia-reperfusion-injury
#5
Arun Samidurai, Fadi N Salloum, David Durrant, Olga B Chernova, Rakesh C Kukreja, Anindita Das
BACKGROUND: Enhanced mammalian target of rapamycin (mTOR) signaling contributes to the pathogenesis of diabetes and plays a critical role in myocardial ischemia/reperfusion (I/R) injury. Rapatar is a novel nanoformulated micellar of rapamycin, a putative inhibitor of mTOR, that have been rationally designed to increase water solubility of rapamycin in order to facilitate oral administration and enhance bioavailability. We examined the effect of Rapatar in improving metabolic status and protection against myocardial I/R injury in type 2 diabetic (T2D) mice...
October 1, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28942514/intrauterine-hyperglycemia-induced-inflammatory-signalling-via-the-receptor-for-advanced-glycation-end-products-in-the-cardiac-muscle-of-the-infants-of-diabetic-mother-rats
#6
Ritsuko Kawaharada, Haruna Masuda, Zhenyi Chen, Eric Blough, Tomoko Kohama, Akio Nakamura
PURPOSE: Gestational diabetes is associated with increased risk to the health of the mother and her offspring. In particular, the infants of diabetic mothers (IDMs) exhibit elevated levels of preterm birth, macrosomia, hypoglycemia, hypocalcemia, and cardiomyopathy. We have previously reported that IDMs showed abnormalities in cardiac Akt-related insulin signalling, and that these deficiencies in Akt-related signalling were attenuated by supplementing the maternal diet with fish-oil. Herein, we investigated whether the eicosapentaenoic acid (EPA) found in fish oil can be used to attenuate diabetes associated impairments in cardiomyocyte signalling...
September 23, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28941626/deletion-of-protein-tyrosine-phosphatase-1b-obliterates-endoplasmic-reticulum-stress-induced-myocardial-dysfunction-through-regulation-of-autophagy
#7
Shuyi Wang, Xiyao Chen, Sreejayan Nair, Dongdong Sun, Xiaoming Wang, Jun Ren
Endoplasmic reticulum (ER) stress has been demonstrated to prompt various cardiovascular risks although the underlying mechanism remains elusive. Protein tyrosine phosphatase-1B (PTP1B) serves as an essential negative regulator for insulin signaling. This study examined the role of PTP1B in ER stress-induced myocardial anomalies and underlying mechanism involved with a focus on autophagy. WT and PTP1B knockout mice were subjected to the ER stress inducer tunicamycin (1mg/kg). Cardiac function was evaluated with echocardiography and an Ion-Optix MyoCam system...
September 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28934640/continuous-longitudinal-infusion-of-rhigf-1-rhigfbp-3-in-extremely-preterm-infants-evaluation-of-feasibility-in-a-phase-ii-study
#8
Ingrid Hansen-Pupp, Ann Hellström, Mohamed Hamdani, Adina Tocoian, Nerissa C Kreher, David Ley, Boubou Hallberg
OBJECTIVE: To evaluate the feasibility of continuous longitudinal intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) for prevention of retinopathy of prematurity and other complications in extremely preterm infants (<28weeks' gestational age), based on initial sections of a phase II randomized controlled trial. DESIGN: The phase II trial was designed in four sections (A-D); we report pharmacokinetic and adverse events (AEs) data pooled for Sections B and C...
August 31, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/28928113/pdk4-inhibits-cardiac-pyruvate-oxidation-in-late-pregnancy
#9
Laura X Liu, Glenn C Rowe, Steven Yang, Jian Li, Federico Damilano, Mun Chun Chan, Wenyun Lu, Cholsoon Jang, Shogo Wada, Michael Morley, Michael Hesse, Bernd K Fleischmann, Joshua Rabinowitz, Saumya Das, Anthony Rosenzweig, Zoltan Arany
Rationale: Pregnancy profoundly alters maternal physiology. The heart hypertrophies during pregnancy, but its metabolic adaptations are not well understood. Objective: To determine the mechanisms underlying cardiac substrate use during pregnancy. Methods and Results: We use here (13)C-glucose, (13)C-lactate, and (13)C-fatty acid tracing analyses to show that hearts in late pregnant mice increase fatty acid uptake and oxidation into the tricarboxylic acid (TCA) cycle, while reducing glucose and lactate oxidation...
September 19, 2017: Circulation Research
https://www.readbyqxmd.com/read/28917508/insulin-dependent-metabolic-and-inotropic-responses-in-the-heart-are-modulated-by-hydrogen-peroxide-from-nadph-oxidase-isoforms-nox2-and-nox4
#10
Benjamin Steinhorn, Juliano L Sartoretto, Andrea Sorrentino, Natalia Romero, Hermann Kalwa, E Dale Abel, Thomas Michel
RATIONALE: Hydrogen peroxide (H2O2) is a stable reactive oxygen species (ROS) that has long been implicated in insulin signal transduction in adipocytes. However, H2O2's role in mediating insulin's effects on the heart are unknown. OBJECTIVE: We investigated the role of H2O2 in activating insulin-dependent changes in cardiac myocyte metabolic and inotropic pathways. The sources of insulin-dependent H2O2 generation were also studied. METHODS AND RESULTS: In addition to the canonical role of insulin in modulating cardiac metabolic pathways, we found that insulin also inhibited beta adrenergic-induced increases in cardiac contractility...
September 14, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28888936/%C3%AE-arrestin-2-is-involved-in-irisin-induced-glucose-metabolism-in-type-2-diabetes-via-p38-mapk-signaling
#11
Yaling Pang, Haihui Zhu, Jianqin Xu, Lihua Yang, Lingjiao Liu, Jing Li
Type 2 diabetes mellitus (T2DM) is a common metabolic disease worldwide. It has been reported that irisin play regulatory role in glucose metabolism in T2DM. However, the underlying mechanism involved in that is not completely known. Herein, we determined the novel role of β-arrestin-2 in irisin-induced glucose utilization in diabetes. Effects of irisin and β-arrestin-2 on glucose utilization were investigated in a rat model of diabetes and in diabetic C2C12 cells in vitro. Results showed that irisin had positive role in glucose metabolism via regulating glucose tolerance as well as uptake in cardiac and skeletal muscle tissues, as evidenced by IPGTT, 2-deoxyglucose uptake and plasma membrane GLUT-4 assay...
September 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28867181/insulin-upregulates-grim-19-and-protects-cardiac-mitochondrial-morphology-in-type-1-diabetic-rats-partly-through-pi3k-akt-signaling-pathway
#12
Yong-Guang Li, Zhi-Feng Dong, Kan-Kai Chen, Ya-Ping He, Xiao-Yan Dai, Shuai Li, Jing-Bo Li, Wei Zhu, Meng Wei
Insulin is involved in the development of diabetic heart disease and is important in the activities of mitochondrial complex I. However, the effect of insulin on cardiac mitochondrial nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 subunit of retinoic-interferon-induced mortality 19 (GRIM-19) has not been characterized. The aim of this study was to investigate the effect of insulin on the mitochondrial GRIM-19 in the hearts of rats with streptozotocin (STZ)-induced type 1 diabetes. Protein changes of GRIM-19 were evaluated by western blotting and reverse transcription-quantitative polymerase chain reaction...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28844956/interleukin-6-deficiency-facilitates-myocardial-dysfunction-during-high-fat-diet-induced-obesity-by-promoting-lipotoxicity-and-inflammation
#13
Fan Chen, Dandan Chen, Xinmei Zhao, Shuai Yang, Zhe Li, Daniel Sanchis, Liang Jin, Xizhe Qiang, Kaiye Wang, Yitao Xu, Yubin Zhang, Junmei Ye
OBJECTIVE: Obesity is associated with metabolic disorder and chronic inflammation that plays a crucial role in cardiovascular diseases. IL-6 is involved in regulating obesity-related lipid metabolism and inflammation. In this study, we sought to determine the role of IL-6 in high-fat diet (HFD)-induced cardiomyopathy and explore the signaling pathway. METHODS: Female, 5-week-old IL-6 knockout (KO) and littermate mice were fed a normal diet (ND, 10% fat) or HFD (45% fat) for 14 weeks...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28838041/the-role-of-mineralocorticoid-receptor-signaling-in-the-cross-talk-between-adipose-tissue-and-the-vascular-wall
#14
Guanghong Jia, Annayya R Aroor, James R Sowers
Vascular dysfunction and impaired endothelial mediated relaxation are powerful underlying abnormalities in the pathogenesis of hypertension, coronary heart disease, and stroke. Obesity, type 2 diabetes mellitus, and other metabolic abnormalities are associated with activation of mineralocorticoid receptor (MRs) in the vasculature and adipose tissue. While MR signaling is involved in the normal physiological differentiation and maturation of adipocyte, enhanced activation of MRs also contributes to increase oxidative stress, release of pro-inflammatory adipokines, and dysregulation of adipocyte autophagy...
July 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28830979/alterations-in-fatty-acid-metabolism-and-sirtuin-signaling-characterize-early-type-2-diabetic-hearts-of-fructose-fed-rats
#15
Phing-How Lou, Eliana Lucchinetti, Katrina Y Scott, Yiming Huang, Manoj Gandhi, Martin Hersberger, Alexander S Clanachan, Hélène Lemieux, Michael Zaugg
Despite the fact that skeletal muscle insulin resistance is the hallmark of type-2 diabetes mellitus (T2DM), inflexibility in substrate energy metabolism has been observed in other tissues such as liver, adipose tissue, and heart. In the heart, structural and functional changes ultimately lead to diabetic cardiomyopathy. However, little is known about the early biochemical changes that cause cardiac metabolic dysregulation and dysfunction. We used a dietary model of fructose-induced T2DM (10% fructose in drinking water for 6 weeks) to study cardiac fatty acid metabolism in early T2DM and related signaling events in order to better understand mechanisms of disease...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28830209/puerarin-improves-vascular-insulin-resistance-and-cardiovascular-remodeling-in-salt-sensitive-hypertension
#16
Chunxiang Tan, Aimei Wang, Chan Liu, Yao Li, Yuepin Shi, Ming-Sheng Zhou
Puerarin is an isoflavonoid isolated from the Chinese herb, Kudzu roots (also known as Gegen), which has been widely used for the treatment of hypertensive diseases and diabetic mellitus in traditional Chinese medicine. Dahl salt-sensitive (DS) rat is a genetic model of salt-sensitive hypertension with cardiovascular injury and vascular insulin resistance. Here, we investigated whether puerarin improved vascular insulin resistance and attenuated cardiac and aortic remodeling in salt-sensitive hypertension. DS rats were given a normal (NS) or high salt diet (HS) for five weeks...
2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28821796/cathepsin-k-knockout-protects-against-cardiac-dysfunction-in-diabetic-mice
#17
Rui Guo, Yinan Hua, Olivia Rogers, Travis E Brown, Jun Ren, Sreejayan Nair
Diabetes is a major risk factor for cardiovascular disease and the lysosomal cysteine protease cathepsin K plays a critical role in cardiac pathophysiology. To expand upon our previous findings, we tested the hypothesis that, knockout of cathepsin K protects against diabetes-associated cardiac anomalies. Wild-type and cathepsin K knockout mice were rendered diabetic by streptozotocin (STZ) injections. Body weight, organ mass, fasting blood glucose, energy expenditure, cardiac geometry and function, cardiac histomorphology, glutathione levels and protein levels of cathepsin K and those associated with Ca(2+) handling, calcineurin/NFAT signaling, insulin signaling, cardiac apoptosis and fibrosis were determined...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28781146/the-impact-of-foxo-1-to-cardiac-pathology-in-diabetes-mellitus-and-diabetes-related-metabolic-abnormalities
#18
Dimitry A Chistiakov, Alexander N Orekhov, Yuri V Bobryshev
Diabetic heart pathology has a serious social impact due to high prevalence worldwide and significant mortality/invalidation of diabetic patients suffered from cardiomyopathy. The pathogenesis of diabetic and diabetes-related cardiomyopathy is associated with progressive loss and impairment of cardiac function due to adverse effects of metabolic, prooxidant, proinflammatory, and pro-apoptotic stress factors. In the adult heart, the transcriptional factor forkhead box-1 (FOXO-1) is involved in maintaining cardiomyocytes in the homeostatic state and induction of their adaptation to metabolic and pro-oxidant stress stimuli...
August 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28743802/enhancing-natriuretic-peptide-signaling-in-adipose-tissue-but-not-in-muscle-protects-against-diet-induced-obesity-and-insulin-resistance
#19
Wei Wu, Fubiao Shi, Dianxin Liu, Ryan P Ceddia, Robert Gaffin, Wan Wei, Huafeng Fang, E Douglas Lewandowski, Sheila Collins
In addition to controlling blood pressure, cardiac natriuretic peptides (NPs) can stimulate lipolysis in adipocytes and promote the "browning" of white adipose tissue. NPs may also increase the oxidative capacity of skeletal muscle. To unravel the contribution of NP-stimulated metabolism in adipose tissue compared to that in muscle in vivo, we generated mice with tissue-specific deletion of the NP clearance receptor, NPRC, in adipose tissue (Nprc(AKO) ) or in skeletal muscle (Nprc(MKO) ). We showed that, similar to Nprc null mice, Nprc(AKO) mice, but not Nprc(MKO) mice, were resistant to obesity induced by a high-fat diet...
July 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28739173/lipid-droplet-proteins-and-metabolic-diseases
#20
REVIEW
Shimeng Xu, Xuelin Zhang, Pingsheng Liu
Lipid droplets (LDs) are ubiquitous cellular organelles for lipid storage which are composed of a neutral lipid core bounded by a protein decorated phospholipid monolayer. Although lipid storage is their most obvious function, LDs are far from inert as they participate in maintaining lipid homeostasis through lipid synthesis, metabolism, and transportation. Furthermore, they are involved in cell signaling and other molecular events closely associated with human disease such as dyslipidemia, obesity, lipodystrophy, diabetes, fatty liver, atherosclerosis, and others...
July 21, 2017: Biochimica et Biophysica Acta
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