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Insulin signaling heart

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https://www.readbyqxmd.com/read/28928113/pdk4-inhibits-cardiac-pyruvate-oxidation-in-late-pregnancy
#1
Laura 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
#2
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 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28915960/pleiotropic-effects-of-metformin-to-rescue-statin-induced-muscle-injury-and-insulin-resistance-a-proposed-mechanism-and-potential-clinical-implications
#3
Nicholas W Carris, Srinivas M Tipparaju, David J Magness, Kalyan C Chapalamadugu, Ronald R Magness
The 2013 American Heart Association Blood Cholesterol Guidelines increased the number of patients recommended for statin therapy in the United States to 56million. Two common statin side effects are muscle pain, referred to as "statin-associated muscle symptoms", and increased risk for new onset type-2-diabetes mellitus. Up to 25% of statin users report muscle symptoms resulting in many patients being switched to lower dose or lower potency statins, or refusing statins altogether. The most likely signaling mechanisms for statin-associated muscle symptoms overlaps with the proposed mechanism of statin-induced insulin resistance...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28867579/socs2-exacerbates-myocardial-injury-induced-by-ischemia-reperfusion-in-diabetic-mice-and-h9c2-cells-through-inhibiting-the-jak-stat-igf-1-pathway
#4
Mengting Sheng, Zirui Huang, Liming Pan, Min Yu, Cai Yi, Lin Teng, Ling He, Chen Gu, Chunli Xu, Junming Li
AIMS: This study aimed to investigate potential candidates and molecular mechanisms of myocardial ischemia/reperfusion (I/R) injury (MIRI) in type 2 diabetes mellitus. MAIN METHODS: Type 2 diabetic and myocardial I/R mouse models were established with a high fat-diet (HFD) for 24weeks and subjecting to global ischemia/reperfusion for 1h/3h, respectively. Microarray analysis was applied to screen differentially expressed genes (DEGs) in the hearts of these mice. Moreover, H9c2 cells were treated with high glucose (HG) and/or hypoxia and reoxygenation (H/R)...
August 31, 2017: Life Sciences
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
#5
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...
August 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28851613/characterization-of-the-visfatin-gene-and-its-expression-pattern-and-effect-on-3t3-l1-adipocyte-differentiation-in-chickens
#6
Zhuanjian Li, Yongcai Wang, Xiaoxiao Tian, Pengfei Shang, Hong Chen, Xiangtao Kang, Yadong Tian, Ruili Han
Visfatin is a newly identified adipocytokine that plays an important role in the determination of fat traits. In this study, we investigated the characterization of visfatin and the relationship between gene expression and chicken development to provide a theoretical basis for studying visfatin functions. The main results are summarized as follows: The 1482-bp full coding sequence of the visfatin gene of silky fowl was obtained and found to encode 493 amino acids. This gene contains 26 phosphorylation sites and a conserved domain of the NAPRTase family but no signal peptide sequence...
October 20, 2017: Gene
https://www.readbyqxmd.com/read/28844956/interleukin-6-deficiency-facilitates-myocardial-dysfunction-during-high-fat-diet-induced-obesity-by-promoting-lipotoxicity-and-inflammation
#7
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. At the end of treatment, cardiac function was assessed by echocardiography...
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
#8
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
#9
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
#10
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...
August 22, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28819004/acute-oxygen-sensing-by-the-carotid-body-from-mitochondria-to-plasma-membrane
#11
Andy J Chang
Maintaining oxygen homeostasis is crucial to the survival of animals. Mammals respond acutely to changes in blood oxygen levels by modulating cardiopulmonary function. The major sensor of blood oxygen that regulates breathing is the carotid body (CB), a small chemosensory organ located at the carotid bifurcation. When arterial blood oxygen levels drop in hypoxia, neuroendocrine cells in the CB called glomus cells are activated to signal to afferent nerves that project to the brainstem. The mechanism by which hypoxia stimulates CB sensory activity has been the subject of many studies over the last 90 years...
August 17, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28781146/the-impact-of-foxo-1-to-cardiac-pathology-in-diabetes-mellitus-and-diabetes-related-metabolic-abnormalities
#12
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/28777829/identification-of-an-early-transcriptomic-signature-of-insulin-resistance-and-related-diseases-in-lymphomonocytes-of-healthy-subjects
#13
Alice Matone, Eleonora Derlindati, Luca Marchetti, Valentina Spigoni, Alessandra Dei Cas, Barbara Montanini, Diego Ardigò, Ivana Zavaroni, Corrado Priami, Riccardo C Bonadonna
Insulin resistance is considered to be a pathogenetic mechanism in several and diverse diseases (e.g. type 2 diabetes, atherosclerosis) often antedating them in apparently healthy subjects. The aim of this study is to investigate with a microarray based approach whether IR per se is characterized by a specific pattern of gene expression. For this purpose we analyzed the transcriptomic profile of peripheral blood mononuclear cells in two groups (10 subjects each) of healthy individuals, with extreme insulin resistance or sensitivity, matched for BMI, age and gender, selected within the MultiKnowledge Study cohort (n = 148)...
2017: PloS One
https://www.readbyqxmd.com/read/28736261/genetic-disruption-of-the-cardiomyocyte-circadian-clock-differentially-influences-insulin-mediated-processes-in-the-heart
#14
Graham R McGinnis, Yawen Tang, Rachel A Brewer, Manoja K Brahma, Haley L Stanley, Gobinath Shanmugam, Namakkal Soorappan Rajasekaran, Glenn C Rowe, Stuart J Frank, Adam R Wende, E Dale Abel, Heinrich Taegtmeyer, Silvio Litovsky, Victor Darley-Usmar, Jianhua Zhang, John C Chatham, Martin E Young
Cardiovascular physiology exhibits time-of-day-dependent oscillations, which are mediated by both extrinsic (e.g., environment/behavior) and intrinsic (e.g., circadian clock) factors. Disruption of circadian rhythms negatively affects multiple cardiometabolic parameters. Recent studies suggest that the cardiomyocyte circadian clock directly modulates responsiveness of the heart to metabolic stimuli (e.g., fatty acids) and stresses (e.g., ischemia/reperfusion). The aim of this study was to determine whether genetic disruption of the cardiomyocyte circadian clock impacts insulin-regulated pathways in the heart...
September 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28736243/from-insulin-synthesis-to-secretion-alternative-splicing-of-type-2-ryanodine-receptor-gene-is-essential-for-insulin-secretion-in-pancreatic-%C3%AE-cells
#15
Hiroshi Okamoto, Shin Takasawa, Yasuhiko Yamamoto
Increases in the intracellular Ca(2+) concentration in pancreatic islets, resulting from the its mobilization from the intracellular source through the ryanodine receptor, are essential for insulin secretion by glucose. Cyclic ADP-ribose, a potent Ca(2+) mobilizing second messenger synthesized from NAD(+) by CD38, regulates the opening of ryanodine receptor. A novel ryanodine receptor mRNA (the islet-type ryanodine receptor) was found to be generated from the type 2 ryanodine receptor gene by the alternative splicing of exons 4 and 75...
July 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28735097/protecting-the-heart-through-mk2-modulation-toward-a-role-in-diabetic-cardiomyopathy-and-lipid-metabolism
#16
REVIEW
Matthieu Ruiz, Lise Coderre, Bruce Gordon Allen, Christine Des Rosiers
Various signaling pathways have been identified in the heart as important players during development, physiological adaptation or pathological processes. This includes the MAPK families, particularly p38MAPK, which is involved in several key cellular processes, including differentiation, proliferation, apoptosis, inflammation, metabolism and survival. Disrupted p38MAPK signaling has been associated with several diseases, including cardiovascular diseases (CVD) as well as diabetes and its related complications...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28722106/anti-inflammatory-effects-of-exercise-role-in-diabetes-and-cardiovascular-disease
#17
REVIEW
Bente Klarlund Pedersen
BACKGROUND: Persistent inflammation is involved in the pathogenesis of chronic diseases such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). AIMS: The aim of this review was to provide the reader with an update of the mechanisms whereby exercise-induced cytokines may impact cardiometabolic diseases. RESULTS: Evidence exists that interleukin (IL)-1β is involved in pancreatic β-cell damage, whereas TNF-α is a key molecule in peripheral insulin resistance...
July 19, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28714796/effect-of-bariatric-surgery-on-heart-failure
#18
Marcela Rodriguez Flores, Carlos Aguilar Salinas, Marie-Eve Piché, Audrey Auclair, Paul Poirier
Obesity increases the risk of heart failure (HF), which continues to be a significant proportion of all cardiovascular diseases and affects increasingly younger populations. The cross-talk between adipose and the heart involves insulin resistance, adipokine signaling and inflammation, with the capacity of adipose tissue to mediate hemodynamic signals, promoting progressive cardiomyopathy. Areas covered: From a therapeutic perspective, there is not yet a single obesity-related pathway that when addressed, can ameliorate cardiomyopathy in obese patients and this is a matter of ongoing research...
August 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28708941/regulation-of-the-insulin-akt-signaling-pathway-and-glycolysis-during-dehydration-stress-in-the-african-clawed-frog-xenopus-laevis
#19
Cheng-Wei Wu, Shannon N Tessier, Kenneth B Storey
Estivation is an adaptive stress response utilized by some amphibians during periods of drought in the summer season. In this study, we examine the regulation of the insulin signaling cascade and glycolysis pathway in the African clawed frog Xenopus laevis during dehydration stress induced state of estivation. We show that in the brain and heart of X. laevis, dehydration reduces the phosphorylation of the insulin growth factor-1 receptor (IGF-1R), and this is followed by similar reductions in the phosphorylation of the Akt and mechanistic target of rapamycin (mTOR) kinase...
July 14, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28698617/loss-of-md1-exacerbates-pressure-overload-induced-left-ventricular-structural-and-electrical-remodelling
#20
Jianye Peng, Yu Liu, Xiaoju Xiong, Congxin Huang, Yang Mei, Zhiqiang Wang, Yanhong Tang, Jing Ye, Bin Kong, Wanli Liu, Teng Wang, He Huang
Myeloid differentiation protein 1 (MD1) has been implicated in numerous pathophysiological processes, including immune regulation, obesity, insulin resistance, and inflammation. However, the role of MD1 in cardiac remodelling remains incompletely understood. We used MD1-knockout (KO) mice and their wild-type littermates to determine the functional significance of MD1 in the regulation of aortic banding (AB)-induced left ventricular (LV) structural and electrical remodelling and its underlying mechanisms. After 4 weeks of AB, MD1-KO hearts showed substantial aggravation of LV hypertrophy, fibrosis, LV dilation and dysfunction, and electrical remodelling, which resulted in overt heart failure and increased electrophysiological instability...
July 11, 2017: Scientific Reports
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